Search

By all measures attempted, scientific literacy of the American public is sadly wanting. The vast majority of our secondary school children and adults have no knowledge of most of the basic terms or concepts of science. The reasons for this shortcoming are many but prominent among them are sadly deficient texts, teachers untrained in the subject matter they teach, and college and university scientists who divorce themselves from the problem, although probably deploring it. Our institutions are no aid. They reward scientific productivity (read: number of papers published per year and research dollars), not teaching. Some suggested cures are production of better texts, training of science teachers in the field in which they teach, and, most importantly, involvement of scientists in the process. We must be willing to spend some of our time with secondary school pupils and their teachers. All will gain from the experience.

Sodium excretion was studied following experimental elevation of cerebrospinal fluid (CSF) sodium in heterozygous and homozygous (DI) Brattleboro rats given exogeneous antidiuretic hormone. Sodium excretion increased 4.5-fold in heterozygous and 3.5-fold in DI rats. The natriuresis in both groups was rapid in onset and occurred with a simultaneous kaliuresis. Blood pressure increased approximately 10 mmHg in the heterozygous but not in the DI rats. Accordingly, increased blood pressure may contribute to the natriuresis but is not the sole mechanism. Plasma renin concentration did not change in the DI rats during high Na CSF infusion, and chronic bilateral renal denervation did not abolish the natriuresis. Glomerular filtration rate increased during the high Na period in both the intact and renally denervated rats. These data provide evidence that a natriuretic mechanism exists that is not mediated by changes in antidiuretic hormone, renal nerve activity, mean arterial pressure, aldosterone, or angiotensin II, and thus may be due to another circulating substance or natriuretic hormone. This hormone may act totally or in part by increasing glomerular filtration rate.

Drinking rates were measured in the euryhaline fish Fundulus heteroclitus in the presence and absence of angiotensin II or its competitive inhibitor P-113 and converting enzyme inhibitor (SQ20881). Angiotensin stimulated drinking in Fundalus adapted to salt- or freshwater. More significant, P-113 decreased drinking rates in saltwater-adapted fish and to ones acutely exposed to saltwater. SQ20881 was also effective in inhibiting drinking. These data are interpreted to support the hypothesis that endogenously produced angiotensin is a physiological stimulus for drinking in fish.

Arterial blood pressure, urine flow rate, and plasma and urine electrolytes were measured in the aglomerular goosefish (L. americanus) before, during, and after the intravenous infusion of angiotensin II (from 5 to 280 ng/min.kg body wt). Increases in arterial blood pressure were directly related to the logarithm of the angiotensin infusion rate (r = 0.62, P less than 0.005). Angiotensin also increased urine flow from 0.676 +/- 0.065 to 0.755 +/- 0.068 ml/h.kg body wt (P less than 0.005) and Na excretion from 41.0 +/- 5.5 to 54.4 +/- 7.0 mumol/h.kg body wt (P less than 0.001). In 17 of the 19 fish infused with angiotensin the diuretic and natriuretic effects were directly related to the logarithm of the infusion rate (r = 0.44, P less than 0.04 and r = 0.51, P less than 0.02, respectively). There was no relationship between the pressor and the diuretic or natriuretic effects of angiotensin II. These results are consistent with inhibitory effects of angiotensin on solute transport by aglomerular tubules.

Rat kidney contains six forms of renin, which are in different proportion from those found in plasma. We tested the hypothesis that differential removal and production of the forms might explain the differences between stored and circulating renins. In one group of rats, the six forms of renin were measured in plasma, 10 min after hemorrhage, or after aortic constriction. Plasma was run on an isoelectric focusing gel, and the six peaks of renin activity were expressed either as angiotensin I per hour per milliliter or as a percentage of the total plasma renin concentration. After hemorrhage or aortic constriction, the concentration of each form was significantly increased; the profile of circulating renin was significantly modified, showing an increase in proportion of form 2 and a decrease of forms 4, 5, and 6. In a second group, the disappearance of each form was measured 0 to 100 min after nephrectomy and fitted a two-exponential decay curve. Interpreted as a two-pool system with degradation from pool 1, the degradation rate decreased progressively, going from form 1 to 6. In a third group, arterial and renal venous blood were collected. The profile of secreted renin was calculated from the arterial venous difference. This profile fitted the prediction of the two-compartment model. Our data support the hypothesis that the proportion of each circulating renin form is the result of a balance between the rate of production of renin of constant composition and the degradation of the six forms at different rates.

Six forms of renin have been described in rat kidney. Different stimuli resulted in secretion of unique profiles of those forms. We studied their storage and secretion in the two-kidney, one-clip Goldblatt hypertensive rat (GHR). Renal venous blood, kidney homogenates, and incubation media from cortical slices were subjected to isoelectric focusing. In all samples tested, six peaks of renin activity were found with isoelectric points at pH 5.90, 5.70, 5.40, 5.20, 5.00, and 4.80. The quantity of renin activity for each form was expressed as a percentage of the total recovered from the gel. In control kidneys the profile of renin stored and that released by in vitro slices were similar. However, in plasma, the percentage of renin focusing at the more basic pH was decreased. This is in agreement with other work showing that the liver removes the more basic forms more rapidly than the acidic forms. The clipped kidney of GHR secreted, both in vivo and in vitro, a profile of renin forms that was significantly different from the control kidney. The difference was expressed by an increase in the secretion of the more acidic forms by the clipped kidney. It is hypothesized that changes in the secretory profile of renin may reflect changes in storage and synthesis of those forms.

The alteration of renin release by alpha- and beta-adrenoceptors located on the juxtaglomerular cells has been shown to be temperature sensitive in nonhibernating mammals. These experiments investigate the effects of temperature on renin secretion by cortical slices of kidneys from the thirteen-lined ground squirrel Spermophilus tridecemlineatus. At 37 degrees C, beta-stimulation (isoproterenol 10(-7) M) increased the release of renin by slices taken from nonhibernating ground squirrels but had no effect on those taken from hibernating squirrels. The alpha-agonist phenylephrine (10(-5) M) had no effect on slices from nonhibernating squirrels but enhanced the release rate in those from hibernating ground squirrels, providing the first evidence of in vitro stimulation of renin release by an alpha-agonist. When incubated at 11 degrees C, kidney slices from both hibernating and nonhibernating animals were unresponsive to both alpha- and beta-agonists until incubation times were doubled. Under these prolonged conditions, phenylephrine again stimulated renin release. These results indicate that both in vitro and in vivo cooling alter the responses of alpha- and beta-adrenoceptors to renin-releasing stimuli.

The presence of a renin-angiotensin system was demonstrated in the poikilotherm Ambystoma tigrinum, commonly called the tiger salamander. Standard radioimmunoassay techniques were employed to measure the intrarenal renin activity (IRA) and the plasma renin activity (PRA) of A. tigrinum kept at either 5 or 20 degrees C. Basal IRA and PRA values were not affected by the temperature at which the animals were maintained. Intraperitoneal injection of the beta-adrenergic agonist isoproterenol, however, increased PRA only in those animals maintained at 20 degrees C. This is consistent with the hypothesis of a temperature sensitivity of the renal adrenergic system in vivo. In addition, we were able to demonstrate the existence of a contractile response of Ambystoma vascular smooth muscle to angiotensin II that was blocked by the competitive inhibitor saralasin.

Various parameters of renal function were studied before, during, and after the infusion of physiological increments of angiotensin II directly into one renal artery of anesthetized dogs. During water diuresis and during antidiuresis induced with exogenous antidiuretic hormone (ADH), angiotensin II consistently reduced UNaV, UKV, and CPAH, and increased the filtration fraction in the infused kidney. Urinary osmolality was increased only in the presence of ADH, while during water diuresis angiotensin II had no apparent effect on urinary osmolality or flow rate. During saline diuresis, a mean increment of angiotensin II concentration of 14 pg/ml was sufficient to significantly reduce UNaV and urinary flow rate. Changes in CCr, CPAH, and filtration fraction did not correlate with changes in sodium excretion, and intracortical distribution of blood flow remained unaltered. These data support the hypothesis that normal circulating levels of angiogensin II play a direct renal role in the control of sodium, potassium, and water homeostasis, and that angiotensin II exerts a direct, stimulatory effect on tubular sodium reabsorption independent of changes in GFR, RPF, filtration fraction, or intracortical distribution of blood flow.

Six forms of renin with different isoelectric points (pIs) have been described in rats. This study was designed to determine if any of the renin forms have different biological activities. Each form of rat renin was semipurified and injected intravenously or intraventricularly in Sprague-Dawley rats anesthetized with pentobarbital sodium or Inactin. Changes in blood pressure (BP), renal function, sodium, and water excretion were observed, before and following equipressor doses; the peak response of BP was similar for all forms. However, the half-lives were significantly different. Form 4 (pI = 5.2) caused a significant increase in urine flow, Na, and K excretion, and urinary osmolality when given intravenously. The other forms were without significant effect. Infusion of converting enzyme inhibitor not only completely blocked the BP response, but also prevented the natriuresis and diuresis. This was observed in rats anesthetized with pentobarbital sodium or Inactin. Intraventricular infusions resulted in a diuresis and natriuresis when form 6 (pI = 4.8) was infused, but not with other forms. BP remained unchanged throughout. This study presents evidence that functional differences exist between renin forms.

Hepatic clearance of renin in anesthetized dogs was measured during aortic constriction and after nephrectomy. Aortic constriction caused a transient increase in the hepatic extraction ratio for renin (ER) from 0.34 +/- 0.05 to 0.52 +/- 0.05, whereas nephrectomy caused the ER to decrease with time. Isoelectric focusing of plasma samples over an average pH gradient of 4.0-6.2 yielded several peaks of renin activity. Peaks focusing above pH 5.0 were combined and arbitrarily classified as basic renin, whereas peaks below pH 5.0 were classified as acidic renin. In each period the ER for basic renin was significantly greater than that for acidic renin. The proportion of basic renin was transiently increased at 10 min (59 +/- 4%) compared with control (41 +/- 4%). This contributed to the increased ER after constriction. The decreased ER after nephrectomy, however, was not solely due to differential removal of these forms. We conclude that hepatic clearance of renin is partly a function of the type of renin secreted by the kidney, which in turn may change with the duration of the secretory stimulus.

This study was designed to evaluate the physiological importance of cardiopulmonary receptors with vagal afferents in controlling renin release during perturbations in blood volume. Intravascular volume of chloralose-anesthetized dogs was expanded by 7.5 ml/kg body wt, with an isotonic isoncotic solution containing 3% dextran for colloid. Volume expansion resulted in a 50% decline in renin secretion. However, volume expansion after bilateral cervical vagotomy, the proposed afferent limb of the reflex, also suppressed renin release. In another group of animals, the left kidney was surgically denervated and the right kidney extirpated, and again infusion suppressed resin release. In all groups, the infusion significantly suppressed renin release when compared to each dog's own control period, as well as when compared to the corresponding time controls. Our data indicate that the renin response to intravascular volume expansion was not mediated solely by the vagi or renal nerves. A combination of intrarenal factors may, however, have been responsible for the suppression of renin release observed. Our results do not support the hypothesis that the renin-angiotensin system is an efferent limb of the cardiopulmonary reflex during adjustments to alterations in blood volume.

The present experiments were designed to determine if an opiate antagonist affects blood pressure in two-kidney one-clip Goldblatt rats. Male Sprague-Dawley rats were divided into three groups. Group 1 received an infusion of saline intraperitoneally via an osmotic pump and left renal artery constriction (RAC). In group 2, rats were treated the same as group 1, except that they received an intraperitoneal infusion of naloxone (100 micrograms/h). Group 3 received the same infusion of naloxone without RAC. Naloxone-infused Goldblatt rats showed a significantly lower systolic blood pressure (SBP) than saline-infused Goldblatt rats (132 +/- 7 vs. 160 +/- 9 mmHg at day 14), but a higher SBP than control (132 +/- 7 vs. 106 +/- 1 mmHg). Infusion of naloxone did not significantly change SBP in normotensive rats. Renal renin activity in the clipped kidney was higher than in the nonclipped kidney in groups 1 and 2. Plasma renin activity (PRA) in both groups of Goldblatt rats was higher than in group 3, but no significant difference was found between the two groups of Goldblatt rats (groups 1 and 2). Naloxone (1.5 microM) did not affect the basal secretion of renin by isolated cortical slices from untreated rats. The present data demonstrate that naloxone significantly attenuates the development of hypertension in two-kidney one-clip rats. The attenuation of blood pressure was not associated with the changes in PRA, renal renin activity, or plasma aldosterone concentrations. The data support the hypothesis that the endogenous opioid system may be involved in the development of renovascular hypertension.

Six forms of renin, distinguishable by their isoelectric focusing characteristics, are found in rat kidney and plasma (forms 1-6, form 1 having the most basic pI). To test the hypothesis that high blood pressure in stroke-prone spontaneously hypertensive rats (SHRSP) is associated with a particular fraction of the renin forms, systolic blood pressure (SBP) and renin profile were measured in SHRSP, normotensive Wistar-Kyoto rats (WKY), and their genetic crosses (F1). Adult SHRSP showed an increase in the proportion of forms 4, 5, and 6 compared with WKY. F1 showed values between SHRSP and WKY. A strong positive correlation was noted between the fraction of the acidic forms of renin and SBP. The mean blood pressure and the fraction of the acidic renin forms in SHRSP and WKY pups also fitted the same regression line. However, no correlation existed between renal renin content (RRC) and SBP. SHRSP pups had a higher RRC than age-matched WKY or F1. RRC in normal adult SHRSP was lower than that in WKY or F1 of the same age. In old animals, SHRSP again showed the highest RRC, and microangiography of the kidney of old SHRSP revealed a loss of fine vascularity with few visible glomeruli. These results indicate that the established phase of hypertension in SHRSP is associated with an increased proportion of the acidic forms of renin, which may have a unique role in the establishment or maintenance of hypertension. It is also suggested that high RRC in the early developmental stage plays a role in the developing phase of hypertension.

Drinking rates in both marine and freshwater stenohaline fish were studied by measuring the ingestion of polyethylene glycol that had been added to the aquarium water. Two marine species, the long-horned sculpin and the flounder, and three freshwater species, the common goldfish, the mottled sculpin, and the common shiner, were used. Control drinking rates in freshwater fish averaged 0.03-0.1% body wt/h and in marine fish varied between 0.06 and 0.24% body wt/h. Intramuscular injections of angiotensin II (ANG II) stimulated drinking two- to threefold in the two marine species but had no effect on the drinking rate of the freshwater species. Hemorrhage (1-2% of body wt) also stimulated drinking in the two marine species (6- to 10-fold) but did not affect the drinking rate of two freshwater species. Thus exogenous ANG II and hemorrhage stimulate drinking in two marine stenohaline fish as they do in mammals. These responses were absent in the three freshwater fishes studied. However, injection of converting enzyme inhibitor (SQ 20881) or saralasin in order to block endogenous ANG II did not attenuate either basal or hemorrhage-stimulated drinking in the marine fish.

Renin heterogeneity has been described in rat kidney and plasma. In this study, we used the isoelectric focusing method to 1) characterize the adrenal renin forms in control rats, in rats on low- and high-Na diets, and in nephrectomized rats; and 2) examine their resemblance with plasma renin. Active renin (AR) and inactive trypsin-activatable renin (IR) were measured in adrenal homogenates and plasma. Aliquots were subjected to isoelectric focusing gels. Activation with trypsin (5 mg/ml) was performed before or after isoelectric focusing. Results showed that adrenal glands contained AR and IR. The content of adrenal AR increased significantly only in rats fed a low-Na diet. Following anesthesia, nephrectomy, or high-Na intake, the content of adrenal AR and IR was not significantly changed. In plasma, an inverse relationship between AR and IR was found. Adrenal glands contained six forms of AR focusing at the same pH as those of plasma AR but in different proportions. After activation of IR in adrenal glands, two additional renin forms focusing at pH 6.4 and 6.1 were found, whereas after activation of plasma IR, two peaks focusing at pH 5.9 and 4.8 were significantly enhanced. Adrenal AR forms were modified by alterations of salt and water balance differently than plasma AR. These results support the hypotheses of an endogenous production of renin forms by the adrenal gland.

It is now thought that angiotensin II can stimulate antidiuretic hormone (ADH) release in vivo by a direct action in the central nervous system but it is not known whether the locus of stimulation is the hypothalamus or the neurohypophysis or both. Isolated rat neural lobes incubated for 10 min in buffer containing angiotensin II (200 ng/ml or 2 microgram/ml) did not increase ADH release compared to control values, but addition of KCl (60 mM) to the bath markedly stimulated ADH release. However, intact hypothalamoneurohypophysial systems (containing the supraoptic nuclei) incubated with angiotensin II (200 ng/ml or 2 microgram/ml) did show a pronounced stimulation of ADH release. The data support the hypothesis that angiotensin II, at least in vitro, has a central effect on ADH release which is at the level of the hypothalamus.

The in vivo and in vitro rates of renin secretion were measured in kidneys from five groups of dogs in which renal perfusion pressure, salt diet, and neural input were varied to cause large changes in renin secretion rates and renal renin content. It was found that both the in vivo and in vitro secretory rates were proportional to the renal renin content. However, in vitro secretion rates were dependent on content up to 100 ng angiotensin I/mg tissue per h. At higher renin contents no increment in in vitro secretion rate was seen. In vivo secretion rate did not appear to reach a maximum until renal renin content was above 250 ng AI/mg tissue per h. The data are interpreted to support the hypothesis that there exist at least two pools of renin. One releases renin at a fractional rate of about 1.5% of the total content per hour. The other releases renin at a rate dependent on the magnitude of the stimuli acting on the kidneys. It is also suggested that the rate of renin synthesis may be a determinant of the basla rate of renin secretion.

Rat renal cortical slices incubated in vitro released 7.0 +/- 0.5% (mean +/- SE, n=30) of their total renin content into the incubation medium in 1 h. Isoproterenol (10-6 M), a beta-adrenergic agonist, caused a 75 +/- 17% (n=7) increase in renin release from the cortical slices. Treatment of the cortical slices with either cycloheximide or puromycin caused a significant 96.2 +/- 0.34 (n=8) or 98.5 +/- 0.3% (n=5), respectively, inhibition of protein synthesis. After protein synthesis and presumably renin synthesis was blocked with either cycloheximide or puromycin, isoproterenol was still able to increase significantly renin release from the cortical slices despite almost total blockade of protein synthesis. We conclude that a storage pool of renin content is released may exist, since 1) only 7.0 +/- 0.5% of the cortical slice renin content is released each hour, and 2) isoproterenol stimulation of renin release is not acutely dependent on renin synthesis. It is hypothesized that beta-adrenergic stimulation of renin release is elicited from a storage pool of previously synthesized renin.

The release of renin from dog cortical kidney slice preparations incubated in a physiological salt solution can be modulated by alpha- and beta-adrenergic drugs. When given to slices maintained at 37 degrees C, the beta-agonists isoproterenol (ISP) and norepinephrine stimulated renin release from the slices. When the slices were maintained at 20 degrees C, the beta-agonists had no effect on renin release. However, the alpha-agonist phenylephrine inhibited renin release from the slices incubated at 20 degrees C in a dose-dependent manner, whereas its effect on slices incubated at 37 degrees C was less pronounced. The change in response of the slices from beta dominant at 37 degrees C to alpha dominant at 20 degrees C appeared to be a receptor phenomenon. When the cortical slices were incubated with the irreversible alpha-antagonist phenoxybenzamine (POB) at 20 degrees C for 1 h, they were unable to respond to ISP when returned to 37 degrees C. However, POB had no effect on the response of slices to ISP when given at 37 degrees C. It appears that with a decrease in temperature the renal beta-receptors demonstrate properties normally associated with alpha-receptors, namely the potential to be blocked by POB. This may be due to an interconversion of the renal alpha- and beta-adrenoceptors.

The effects of intracerebroventricular (IVT) infusion of angiotensin II (ANG II), the converting enzyme inhibitor SQ 20881, and dopamine were studied in 15 conscious Na-depleted sheep. IVT ANG II (25 ng/min) significantly increased plasma aldosterone (163 +/- 24%) and vasopressin (ADH) (533 +/- 100%). Plasma renin activity (PRA) was decreased to 64 +/- 10% of basal. IVT SQ (1 microgram/min) decreased aldosterone to 70 +/- 10% and ADH to 55 +/- 9% of basal. PRA increased to 124 +/- 10%. There were no significant changes in plasma Na, K, or cortisol levels nor in mean arterial or intracranial pressure after either infusion. Increasing the dose of SQ to 10 micrograms/min resulted in an increased magnitude of change in the same variables. IVT SQ (1 microgram/min) significantly decreased aldosterone level in five nephrectomized sheep. The responses to IVT dopamine (20 micrograms/min) were qualitatively similar to those elicited by IVT SQ. These data support the existence of an endogenous brain renin-angiotensin system (RAS) independent of the renal RAS. ANG II acts centrally to regulate plasma ADH, aldosterone, and PRA levels. The similarity of the responses to SQ and dopamine suggests that a dopaminergic pathway may be involved in these responses.

The effect of Ca concentrations in the incubation medium and of estimated intracellular Ca concentrations on renin release was examined with use of pig renal cortical slices. In addition, the Ca requirement for the epinephrine stimulatory effect and for the ouabain inhibitory action on renin release was also tested. In mediums containing 5.9 mM K, variations in Ca concentration had no effect on renin release. In contrast, when the K concentration was 59 mM, a significant inhibition of renin release was attained with all concentrations of calcium. The inhibition of renin release in high K mediums by Ca was attributed to an increase in the intracellular Ca concentration. In addition, both the stimulatory effect of epinephrine and the inhibitory effect of ouabain on renin release required Ca in the medium. These results support the hypothesis that the control of renin secretion is mediated, in part, by changes in the intracellular concentration of Ca, most likely in the juxtaglomerular cells.

The thermoregulatory role of brain angiotensin II (ANG II) was tested by intracerebroventricular (IVT) infusion of ANG II or the converting enzyme inhibitor SQ 20881 (SQ) in 15 conscious sheep. Deep body temperature decreased 0.30 +/- 0.07 degree C (SE) during the 3-h period of IVT ANG II (25 ng/min) infusion (P less than 0.05) and increased 0.50 +/- 0.13 degree C during IVT SQ (1 microgram/min) infusion (P less than 0.01). To determine whether the rise in body temperature after IVT SQ infusion might be the result of a central renin-angiotensin system (RAS), SQ was infused IVT in five conscious sheep 20 h after bilateral nephrectomy. This resulted in a significant rise in body temperature of 0.28 +/- 0.05 degree C (P less than 0.05). When vasopressin antidiuretic hormone (ADH) was infused intravenously at the same time of IVT SQ infusion, the rise in temperature was depressed, but ADH did not lower the temperature below basal. IVT dopamine (20 micrograms/min) increased body temperature by 0.40 +/- 0.04 degree C (P less than 0.01), which was qualitatively similar to the result with IVT SQ. These data support the hypothesis that endogenous brain ANG II may play a role in thermoregulation. Furthermore, plasma ADH level, regulated in part by brain ANG II, is probably not the mediator of that thermoregulation. The similar effects of IVT dopamine and SQ on body temperature strengthen the hypothesis that dopamine may be involved in the central action of brain ANG II.

Experiments were designed to clarify the factors affecting renin released during in vitro experiments. Kidneys from rat, dog, and pig were used. Experiments were done in which the gas phase was either bubbled through the incubation medium or layered above it. Renin released into the incubation medium disappeared very rapidly when gas was bubbled through the medium. The decline was similar in mediums bubbled with oxygen-CO2 (95%--5%) or nitrogen-CO2 (95%--5%). The half-life of renin activity in the bubbled medium was approximately 15 min in both cases. However, in experiments in which nonbubbled medium was used throughout, renin released into the incubation medium did not disappear after removal of slices. These data are interpreted to mean that the renin released into the incubation medium is inactivated at the air-water interface.

We measured the effect of a constant infusion of rat atrial extract on the glomerular filtration rate (GFR), renal plasma flow (RPF), and plasma renin concentration (PRC) of bioassay rats. The infusion rate of the atrial extract was 0.038 ml/min, which represented 1.25 mg of homogenized atrial tissue/min. To ensure that dead space was cleared, clearance measurements during the atrial extract infusion were not begun until urine flow had increased and 300 microliter of urine had been excreted. In the first series of rats, control GFR was 0.69 +/- 0.05, increased to 1.04 +/- 0.06 during infusion of atrial extract, and then decreased to 0.72 +/- 0.08 ml X min-1 X 100 g-1 during the recovery period. In a second series, RPF was also measured. GFR increased from 0.92 +/- 0.02 to 1.15 +/- 0.05 ml X min-1 X 100 g-1, while RPF was unchanged. In both series, the increase in GFR was statistically significant. Constant infusion of atrial extracts had no significant effect on PRC. These studies provide evidence that an atrial factor can cause a large increase in GFR, which may contribute to the natriuretic effect of atrial extracts.

Six forms of renin are found in the rat kidney. We studied their secretion in renal slices from spontaneously hypertensive stroke-prone rats (SHRSP) and Wistar-Kyoto rats (WKY). Incubation media from renal slices were subjected to isoelectric focusing. Six peaks of renin activity with different isoelectric points were found. The renin concentration of each form was expressed as a percentage of the total recovered from the gel. We established that the forms secreted by renal slices of SHRSP differed from those of WKY: SHRSP slices released a higher proportion of forms focusing at the more acidic pH. The distribution of the six renin forms and of blood pressure (BP) among animals of the F1, F2, and backcross progenies resulting from the cross of SHRSP and WKY rats were studied. In the F1, BP, percentage of renin form 2, and a combination of the percentage of forms 4 + 5 + 6 were intermediate between the parental lines. The backcross rats showed BP and percentages of forms closer to their SHRSP or WKY parent. In the F2, the distribution of BP, percentage of forms 2 and 4 + 5 + 6 take the form of a unimodal distribution with a significantly larger variance than F1. The increase in the correlation between percentage of renin forms and BP, and between renin concentration of BP, in the segregating progenies over that observed in the parental lines and the F1, are support for the hypothesis that these traits are under the control of common genetic mechanisms.

The radioactive microsphere method was used to study the distribution of cortical blood flow in anesthetized dogs during water diuresis and during antidiuresis. Infusion of antidiuretic hormone (ADH) at rates ranging from 0.33 to 0.5 mU/kg-min into dogs previously volume expanded with 3% dextrose resulted in an increase in urinary osmolality and a significant increase in fractional flow in the inner cortex. Mean arterial pressure, glomerular filtration rate, and renal plasma flow were unaltered by the infusion of ADH at these doses, suggesting that absolute, as well as fractional, blood flow to the inner cortex increased in response to ADH. In three additional experiments, termination of an infusion of ADH in hydropenic dogs and subsequent induction of water diuresis was accompanied by a shift in fractional cortical blood flow away from the inner cortex. The redistribution of cortical blood flow in response to ADH at a time when the kidney is producing a more concentrated urine supports the hypothesis that this vascular effect of ADH may have functional significance in the urinary concentration ability of the kidney.

The effects of intracerebroventricular (ICV) infusion of atrial natriuretic factor (ANF; atriopeptin III) on renal function, plasma concentrations of antidiurectic hormone, aldosterone, and plasma renin activity (PRA) were examined in anesthetized rats and sodium-depleted conscious sheep. The results were compared with those obtained by intravenous infusion of the same dose of ANF. In both rats and sheep, urine volume was increased four- to sixfold over basal values by ICV infusion of ANF. The response was not associated with increased excretion of sodium or potassium. However, urine osmolality was decreased, and free water clearance increased. Intravenous infusion of the same dose of ANF was without effect. Neither mean arterial blood pressure nor heart rate was changed by the ICV infusion of ANF. In the sheep, renal plasma flow showed no significant changes and glomerular filtration rate was unaltered with the exception of a single experimental period out of four periods of ICV ANF infusion. Plasma concentration of ADH was decreased and PRA increased, whereas aldosterone levels remained unchanged as a function of ICV ANF. In the rat, the diuretic response to ANF was prevented by continuous intravenous infusion of a subpressor dose of ADH. These results suggest that ANF within the central nervous system inhibits secretion of ADH.