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Chronic insulin infusion in rats increases mean arterial pressure (MAP) by a mechanism dependent on angiotensin II (Ang II). However, the fact that plasma renin activity (PRA) decreases with insulin infusion suggests that Ang II sensitivity is increased and that the parallel reduction in Ang II may partly counteract any hypertensive action of insulin. This study tested that hypothesis by clamping Ang II at baseline levels during chronic insulin infusion. Sprague-Dawley rats were instrumented with artery and vein catheters, and MAP was measured 24 hours per day. In seven angiotensin clamped rats (AC rats), renin-angiotensin II system activity was clamped at normal levels throughout the study by continuous intravenous infusion of the angiotensin-converting enzyme inhibitor benazepril at 5 mg/kg per day (which decreased MAP by 18+/-2 mm Hg) together with intravenous Ang II at 5 ng/kg per minute. Control MAP in AC rats after clamping averaged 99+/-1 mm Hg, which was not different from the 101+/-2 mm Hg measured before clamping Ang II levels. Control MAP in the 8 vehicle-infused rats averaged 105+/-2 mm Hg. A 7-day infusion of insulin (1.5 mU/kg per minute IV) plus glucose (20 mg/kg per minute IV) increased MAP in both groups of rats; however, the increase in MAP was significantly greater in AC rats (12+/-1 versus 5+/-1 mm Hg). This enhanced hypertensive response to insulin in AC rats was associated with a greater increase in renal vascular resistance (153+/-10% versus 119+/-6% of control) and a significant increase in renal formation of thromboxane (149+/-11% of control). Thus, decreased Ang II during insulin infusion limits the renal vasoconstrictor and hypertensive actions of insulin, and this may be caused, at least in part, by attenuation of renal thromboxane production.

Chronic insulin infusion in rats increases mean arterial pressure (MAP) and reduces glomerular filtration rate (GFR), but the mechanisms for these actions are not known. This study tested whether thromboxane synthesis inhibition (TSI) would attenuate the renal and blood pressure responses to sustained hyperinsulinemia. Male Sprague-Dawley rats were instrumented with arterial and venous catheters, and MAP was measured 24 h/day. After 4 days of baseline measurements, endogenous synthesis of thromboxane was suppressed in 7 rats by infusing the thromboxane synthetase inhibitor, U63557A, intravenously (30 microg/kg/min) for the remainder of the experiment; 7 other rats received vehicle. Baseline MAP was not significantly different between vehicle and TSI rats (96 +/- 1 v 99 +/- 1 mm Hg). After 3 days of U63557A or vehicle, a 5-day control period was started, followed by a 7-day infusion of insulin (1.5 mU/kg/min, intravenously). Glucose (22 mg/kg/min, intravenously) was infused along with insulin to prevent hypoglycemia. In the control period, MAP was not different between vehicle and TSI rats (99 +/- 2 v 100 +/- 1 mm Hg), but MAP increased throughout the 7-day infusion period only in the vehicle rats with an average increase in blood pressure of 7 +/- 2 mm Hg. In the control period, GFR was lower in vehicle rats compared with TSI rats (2.5 +/- 0.1 v 3.1 +/- 0.2 mL/min, P = .06), and the decrease to 81% +/- 4% and 91% +/- 6% of control, respectively, during insulin was significant only in the vehicle rats. All variables returned toward control during a 6-day recovery period. These results suggest that full expression of hypertension and renal vasoconstriction during hyperinsulinemia in rats is dependent on a normal ability to synthesize thromboxane.

Recent studies suggest that thromboxane (TX) mediates a significant component of angiotensin II (ANG II)-induced hypertension. However, there is little information to support the hypothesis that this relationship is important during chronic, physiological increases in ANG II, particularly while controlling for variation in endogenous ANG II levels induced by TX inhibition. This study tested that hypothesis in 27 chronically instrumented rats. After baseline measurements, suppression of endogenous TX was induced and maintained throughout the study in 13 rats by i.v. infusion of the TX synthesis inhibitor (TSI) U63557A: the other 14 rats received vehicle. Baseline mean arterial pressure (MAP) was not different between groups and was unchanged by TSI or vehicle. Continuous inhibition of ANG II production was then initiated in both groups of rats by i.v. infusion of the angiotensin-converting enzyme inhibitor (ACEI) benazepril. ACEI reduced blood pressure similarly in vehicle and TSI rats, from 105 +/- 2 to 91 +/- 2 mm Hg and 103 +/- 1 to 89 +/- 1 mm Hg, respectively. ANG II was then infused at 5 ng.kg-1.min-1 i.v. for 7 days in six rats from each group to restore ANG II activity to baseline levels. This dose increased MAP to 103 +/- 2 and 101 +/- 1 mm Hg in vehicle and TSI rats, respectively, values not different from pre-ACEI levels. Seven TSI rats and eight vehicle rats received a higher dose of ANG II (20 ng.kg-1.min-1 i.v.). After 7 days, MAP was higher in vehicle than in TSI rats (143 +/- 5 versus 120 +/- 4 mm Hg). These results suggest that endogenous TX is an important determinant of MAP in ANG II hypertension but may have a diminished role in blood pressure regulation when ANG II is at normal and subnormal levels.

It is known that endothelin-1 stimulates the release of nitric oxide and prostaglandins in various vascular beds. We designed the present study to analyze the roles of prostaglandins and nitric oxide in the effect of endothelin-1 on the regulation of renal hemodynamics and renin release. We used N omega-nitro-L-arginine methyl ester (L-NAME) and meclofenamic acid to inhibit the production of nitric oxide and prostaglandins, respectively. With a nonfiltering kidney model, renal blood flow was reduced 21% in dogs treated with L-NAME and 18% in dogs treated with meclofenamic acid. Inhibition of nitric oxide and prostaglandins, however, produced opposite effects on estimated glomerular hydraulic pressure: L-NAME increased glomerular hydraulic pressure from 63.1 +/- 0.9 to 64.6 +/- 1.3 mm Hg (P < .01), and meclofenamic acid reduced glomerular hydraulic pressure from 63.3 +/- 1.4 to 59.8 +/- 1.6 mm Hg (P < .01). Endothelin-1 infusion produced a dose-dependent reduction in renal blood flow after blockade of nitric oxide and prostaglandins. The responses of glomerular hydraulic pressure were different in the two groups during endothelin-1 infusion. Endothelin-1 progressively reduced glomerular hydraulic pressure in a dose-dependent fashion in the meclofenamic acid group. However, endothelin-1 slightly increased glomerular hydraulic pressure until the infusion rate reached 5.0 ng/kg per minute. At that rate, endothelin-1 reduced glomerular hydraulic pressure from 63.3 +/- 1.4 to 47.0 +/- 1.4 mm Hg in the meclofenamic acid group (P < .01), a more than 25% reduction, whereas at the same dose, endothelin-1 reduced glomerular hydraulic pressure only less than 2% in the L-NAME group. In addition, blockade of nitric oxide and prostaglandins did not alter the inhibitory effect of endothelin-1 on renin release in the non-filtering kidney. Therefore, the present study demonstrates that the release of nitric oxide and prostaglandins might modulate the effects of endothelin-1 on the renal circulation. The present findings suggest that the differential vasoconstrictive effects of endothelin-1 on preglomerular and postglomerular vessels are associated with its stimulation of nitric oxide and prostaglandin production.

We investigated why resting heart rate is elevated in dogs fed a high saturated fat diet for 12.7 +/- 1.8 wk. Obese dogs exhibited elevated body weight (59%), blood pressure (14%), and heart rate (25%). Differences in resting heart rate (control, 58 +/- 5 beats/min; obese, 83 +/- 7 beats/min) were abolished after hexamethonium, indicating an autonomic mechanism. Hexamethonium also reduced blood pressure in obese (20 +/- 4 mmHg) but not control (9 +/- 6 mmHg) animals. Propranolol did not affect heart rate in either group, excluding a beta-adrenergic mechanism. Subsequent administration of atropine increased heart rate more in control than in obese dogs (110 +/- 9 vs. 57 +/- 11 beats/min). The sensitivity of the cardiac limb of the baroreflex (Oxford method) was reduced by 46% in the obese group, confirming impairment of the parasympathetic control of heart rate. The standard deviation of blood pressure measurements was normal when expressed as a percentage of the mean arterial blood pressure (control, 11.2 +/- 0.4%; obese, 11.2 +/- 0.5%). Our results indicate that the development of obesity in dogs fed a high saturated fat diet is accompanied by an attenuated resting and reflex parasympathetic control of heart rate.

Recent studies have shown that faecal residue (dry weight) and Na and K increase with increasing levels of dietary fibre, an effect which may be related to unstirred layers that slow absorption and the flow rate of chyme through the gastrointestinal tract. Salts of Na are the primary osmotic components of chyme and influence both retention of fluid in the bowel and transit of fluid from the small to the large intestine. The present study examines the chronic effects of dietary Na and K intake on faecal Na, K and residue excretion. Male Sprague-Dawley rats were given 12-13 g feed/d (control (g/kg): Na 4, K 8.5) for 1 week, followed by a 4-week period where Na or K intake was altered (0.01-3 times control levels). These diets altered chronic (> 1 week) faecal residue excretion and affected Na and K excretion by 8-, 310- and 2100-fold respectively. Low dietary Na reduced faecal Na and residue; K excretion was doubled during week 1, but fell over weeks 2-4 despite a 4-5-fold increase in plasma aldosterone. Chronic high dietary Na increased faecal Na, residue and K despite a 60% decrease in plasma aldosterone. Chronic low dietary K decreased faecal Na, K and residue and plasma aldosterone. Chronic high dietary K did not alter faecal Na and K despite increased faecal residue and a 4-5-fold increase in plasma aldosterone. Faecal water was unchanged by diet, paralleling changes in faecal residue. Analyses of the results provide systematic models of chronic regulation of faecal Na, K and residue excretions. When plasma aldosterone is low (< 160 ng/l), weekly faecal residue excretion is equal to 3.6 g (fibre intake was 2.6-2.7 g/week)+2.6 g/mmol Na, and K excretion is equal to 0.55 mmol/mmol Na. When plasma aldosterone is high (> 1500 ng/l) weekly faecal residue excretion is equal to 2.3 g + 2.6 g/mmol Na, and K excretion is equal to 0.7 mmol/week + 0.55 mmol/mmol Na.

To study the time-dependent changes in the secretion of atrial natriuretic peptide (ANP) in response to chronic stimulation by controlled increments in atrial pressure, we developed methodology for precise control of right atrial pressure (RAP) in dogs by employing an externally adjustable occluder around the pulmonary artery and a servo-control system. During 7 days of servo-control of RAP at 6.3 +/- 0.1 mmHg above control levels (1.3 +/- 0.1 mmHg), the 24-h coefficient of variation in RAP was 1/45 the variation that occurred under control conditions. After 30 min of increased RAP, mean arterial pressure (MAP) was reduced from 101 +/- 4 to 84 +/- 3 mmHg in association with increments in plasma renin activity (PRA) from 0.6 +/- 0.1 to 2.5 +/- 0.9 ng angiotensin I (ANG I).ml-1.h-1 and in the plasma concentrations of ANP, arginine vasopressin (AVP), and epinephrine from 93 +/- 18 to 484 +/- 61 pg/ml, from 0.5 +/- 0.1 to 9.2 +/- 2.4 pg/ml, and from 82 +/- 27 to 585 +/- 133 pg/ml, respectively. In comparison, on day 7 of servo-control of RAP, sodium balance was achieved and MAP remained depressed (82 +/- 4 mmHg) along with sustained increments in both plasma ANP concentration (482 +/- 67 pg/ml) and PRA (1.7 +/- 0.6 ng ANG I.ml-1.h-1); on the other hand, the plasma concentrations of AVP and epinephrine returned to control levels. This quantitative study indicates that ANP secretion does not chronically adapt to stimulation by increased atrial pressure and suggests that the plasma levels of ANP achieved in heart failure markedly increase renal excretory capability and allow fluid balance to be achieved at a substantial fall in renal perfusion pressure.

This study was designed to analyze the acute effects of hyperkalemia on renin release in the normal filtering kidney and the nonfiltering kidney. Plasma K was increased by acute intravenous KCl infusion. In the normal filtering kidney experiment plasma K was 5.7 vs. 3.5 meq/l. Hyperkalemia resulted in a 45% increase in renal blood flow (RBF) and a 35% increase in glomerular filtration rate (GFR) at the 120-mmHg pressure level. Renin release was significantly greater in the hyperkalemic group than in the control group (P less than 0.01) with the greatest effect over the lower pressure range. In the nonfiltering kidney experiment plasma K was 6.09 vs. 3.5 meq/l. RBF was 33% greater in the hyperkalemic than in the normokalemic group at the 130-mmHg pressure level. Renin release was also greater in the hyperkalemic group than in the normokalemic group (P less than 0.01). However, unlike the normal filtering kidney experiments, in the nonfiltering kidneys the difference in renin release was most prominent at the highest level of renal perfusion pressure. These experiments demonstrate that acute hyperkalemia can cause renal vasodilation and stimulate renin release in both filtering and nonfiltering kidney preparations and that potassium may affect renin release both through a direct effect on the juxtaglomerular cells and indirectly by affecting delivery of fluid and/or NaCl to the macula densa.

Chronic intravenous infusions of atrial natriuretic peptide (ANP) have been shown to lower mean arterial pressure (MAP) in both normal and hypertensive animals. However, the importance of the renal actions of ANP in mediating this hypotension is unknown. This study was designed to determine whether physiological or pathophysiological increases in intrarenal ANP levels influence long-term control of arterial pressure. ANP was infused into the renal artery of seven conscious, uninephrectomized, chronically instrumented dogs at 1, 2, and 4 ng.kg-1.min-1 for 7 days at each dose, followed by a recovery period. Then ANP was infused intravenously following the same protocol. MAP decreased from 88 +/- 3 to 78 +/- 3 mmHg during intrarenal infusion of 1 ng.kg-1.min-1 ANP; increasing the ANP infusion rate did not result in a further reduction in MAP. Systemic arterial plasma ANP concentration did not change from control (15 +/- 5 pg/ml) during 1 or 2 ng.kg-1.min-1 intrarenal ANP infusion but increased slightly during 4 ng.kg-1.min-1 intrarenal ANP infusion, averaging 53 +/- 11 pg/ml. Renal arterial plasma ANP concentrations were calculated to increase to approximately 120 +/- 5, 248 +/- 11, and 484 +/- 22 pg/ml during 1, 2, and 4 ng.kg-1.min-1 intrarenal ANP infusion, respectively. Intravenous ANP infusion did not alter MAP at 1 ng.kg-1.min-1, but MAP was slightly lower than control during 2 and 4 ng.kg-1.min-1 ANP infusion and remained below control during the postinfusion period.(ABSTRACT TRUNCATED AT 250 WORDS)

Although acute infusions of atrial natriuretic peptide (ANP) often cause natriuresis, these effects are not sustained, possibly because of reductions in arterial pressure or other compensatory adaptations. The aim of this study was to determine whether physiological increases in intrarenal ANP levels cause sustained natriuresis if changes in arterial pressure and other neurohumoral influences that might obscure the renal responses are controlled. Changes in renal function were quantitated during chronic unilateral renal arterial infusion of ANP at rates of 1, 2, and 4 ng.kg-1.min-1 in conscious dogs (n = 7) with the urinary bladder split to allow continuous measurement of renal excretion in the ANP-infused and contralateral, vehicle-infused kidneys. There was no change in mean arterial pressure at any infusion rate. During 1 ng.kg-1.min-1 infusion of ANP for 5 days, the renal excretory responses were small and variable. However, during 2 and 4 ng.kg-1.min-1 ANP infusion for 7 days, sodium excretion averaged 37.2 +/- 10.0 and 134.8 +/- 19.0% greater, respectively, in the ANP-infused kidneys compared with the vehicle-infused kidneys but there were no changes in glomerular filtration rate or effective renal plasma flow. These results demonstrate that when compensatory changes in arterial pressure and neurohumoral factors are controlled, ANP, at physiological concentrations, causes marked increases in renal excretion. This study supports the concept that ANP's effects to increase renal excretory capability could play a role in long-term control of arterial pressure and body fluid homeostasis.

The aims of this study were to determine whether chronic hyperinsulinemia, comparable to that found in obese hypertensives, elevates mean arterial pressure (MAP) or potentiates the hypertensive effects of angiotensin II (ANG II). Studies were conducted in conscious dogs with kidney mass reduced by 70% in order to increase their susceptibility to hypertensive stimuli. Insulin infusion (0.5 or 1.0 mU.kg-1.min-1 iv) for 7 days with plasma glucose held constant raised plasma insulin more than fivefold but did not increase MAP in four dogs on 138 meq/day Na intake. In seven dogs maintained on a high Na intake (319 meq/day), insulin infusion (1.0 mU.kg-1.min-1) for 28 days raised fasting insulin from 9.8 +/- 1.5 to 56-78 microU/ml but did not increase MAP, which averaged 106 +/- 2 mmHg during control and 102 +/- 2 mmHg during 28 days of insulin infusion. Insulin caused transient sodium and potassium retention followed by renal "escape" that was associated with increased glomerular filtration rate (12-27%). Plasma renin activity and plasma aldosterone were not altered by insulin. In five dogs infused with ANG II (2.0 ng.kg-1.min-1) to cause mild hypertension, insulin infusion (1.0 mU.kg-1.min-1) for 6-28 days did not increase MAP further. Thus chronic hyperinsulinemia did not elevate MAP, even when kidney mass was reduced, and did not potentiate the hypertensive effects of ANG II. These findings suggest that additional factors besides hyperinsulinemia per se are responsible for obesity-associated hypertension.

The present study was designed to investigate the mechanisms by which the renin-angiotensin system (RAS) regulates arterial pressure (AP) and renal function during chronic sodium deprivation. Intravenous infusion of the converting enzyme inhibitor SQ 14225 (14 microgram.kg-1.mm-1) for 8 days in 12 sodium-deficient dogs caused a marked decrease in AP from 90 +/- 1 to 67 +/- 2 mmHg and a reduction in glomerular filtration rate (GFR), filtration fraction (FF), and plasma aldosterone concentration (PAC). Despite the fall in AP and GFR, urinary Na excretion and effective renal plasma flow (ERPF) increased above control levels. In four dogs, infusion of aldosterone (200 micrograms/day) for 8 days during continuous SQ 14225 infusion restored PAC to levels above control, but did not significantly change AP or renal function from the values observed during SQ 14225 infusion alone. However, infusion of angiotensin II (AII) (10 or 20 ng.kg-1.min-1) for 5--8 days during continuous SQ 14225 infusion almost completely restored AP and renal function to control levels. These data indicate that the RAS plays a major role in regulating AP, renal hemodynamics, and Na excretion during Na deprivation, probably through the direct effects of AII rather than through changes in PAC.

We examined the relationship between plasma renin activity (PRA) and renal arterial pressure (RAP) during 1) control conditions, 2) acute, and 3) chronic intravenous epinephrine (EPI) infusion (125 ng.kg-1.min-1). In eight conscious uninephrectomized dogs maintained on a normal sodium intake, the renin stimulus-response curve (RSRC) was determined by a stepwise reduction in RAP with an inflatable occluder around the renal artery controlled by a servo unit. The RSRC could be approximated by two lines intersecting at a threshold pressure (approximately 20 mmHg below control RAP). In the high-pressure range, PRA was relatively insensitive to changes in RAP, whereas, below threshold pressure, changes in RAP had large effects on PRA. During acute EPI infusion there was approximately a 40% increase in heart rate (control = 57 +/- 3 beats/min) and hematocrit (control = 30 +/- 1%) in association with a rise in plasma EPI concentration from 73 +/- 16 to 1,413 +/- 100 pg/ml; mean arterial pressure (MAP) was unchanged (94 +/- 3 mmHg). Moreover, EPI acutely increased basal PRA from 0.3 +/- 0.1 to 0.8 +/- 0.3 ng angiotensin I.ml-1.h-1 and shifted the RSRC to the right (increasing threshold pressure 7 mmHg) without altering the slope of the RSRC curve either above or below threshold pressure. In contrast, although plasma EPI concentration and hematocrit remained elevated during chronic EPI infusion, heart rate and basal PRA returned to preinfusion values. In addition, there were no significant long-term changes in MAP or in any of the parameters of the RSRC.(ABSTRACT TRUNCATED AT 250 WORDS)

It has been proposed that arginine vasopressin (AVP) contributes to the regulation of renal sodium excretion by direct intrarenal actions, by neural-hormonal interactions, and via secondary effects of fluid volume retention. The present studies were designed to determine the extent to which the natriuretic effects of AVP are secondary to volume expansion. Three groups of dogs were studied: the first was infused with AVP for 2 weeks in amounts that increased plasma levels from 3 to 15 pg/mL, while water intake was maintained constant by intravenous (iv) water infusion. The second group received the same amount of AVP and was permitted to drink ad libitum. The third group was infused with the same amount of AVP, while total body weight and volume were maintained at a constant level by use of an electronically servo-controlled water infusion system. The results showed a large increase in total body weight (+1.5 kg) and arterial pressure (mean arterial pressure (MAP); +40 mm Hg) in dogs receiving a fixed water intake. This was accompanied by a continuing natriuresis over a 2-week period and severe hyponatremia (115 mEq/L). Dogs allowed ad libitum drinking retained much less fluid (+0.5 kg). MAP was not significantly elevated, and natriuresis did not occur in this group, but hyponatremia was observed (130 mEq/L), and plasma renin activity (PRA) was suppressed. Servo-controlled dogs exhibited no change in MAP, plasma sodium, or PRA, and only a small (-15 mEq) natriuresis occurred on day 1 of AVP infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Three groups of dogs were studied to determine to what extent the suppression of plasma renin activity (PRA), natriuresis, and hyponatremia, seen with chronic elevations of plasma vasopressin (AVP), were caused by volume expansion or some other more direct actions of AVP. The dogs of group 1 (n = 7) were infused with AVP (0.36 ng/kg/min, i.v.) for 2 weeks, while water intake was maintained at a constant level. The dogs of group 2 (n = 6) were permitted to drink ad libitum during AVP infusion. The dogs of group 3 (n = 7) were infused with AVP while total body weight and volume were maintained at a constant level by use of an electronically servocontrolled water infusion system. Group 1, with fixed water intake, retained a large fluid volume (1.4 L), with an associated 36 mm Hg rise in mean arterial blood pressure (MAP). Associated with this hypertension and increased volume were a suppression of PRA and substantial decreases in plasma sodium concentration with increased excretion of sodium. With ad libitum drinking (group 2), only mild volume expansion occurred, with no significant elevations of MAP or changes in sodium excretion. With a volume expansion of 300-400 ml, there was a significant decrease of PRA and plasma sodium concentration. Group 3, servocontrolled dogs, exhibited no change in MAP, plasma sodium concentration, or PRA throughout the 2-week period of AVP infusion. Sodium excretion was mildly elevated only on the first day of AVP infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Physiological levels of arginine vasopressin (AVP) were continuously infused 24 h/day into six dogs for periods ranging from 7 to 34 days. The acute and chronic responses of the mean arterial pressure (MAP), body fluid volumes, renal function indices, plasma electrolyte concentrations, plasma renin activity, and urinary electrolyte and water excretion rates were measured. MAP was unaffected acutely but rose significantly to a peak on day 9 before declining toward control. MAP was significantly and positively correlated with the plasma volume, but had a diphasic correlation with the plasma sodium concentration and the change in total body sodium. The plasma sodium concentration reached a relatively stable plateau that was maintained in spite of large changes in total body water. We conclude that AVP produces only a transient hypervolemic hypertension; that AVP is a natriuretic agent, either directly or indirectly, both acutely and chronically; and that chronically it is a more potent controller of the plasma sodium concentration than of the total body water except in extreme cases.

This study examined the role of increased renal arterial pressure (RAP) in renal escape from the chronic Na-retaining effects of angiotensin II (ANG II). When RAP was allowed to increase during ANG II infusion (5 ng X kg-1 X min-1), urinary Na excretion (UNaV) decreased transiently on the first day but there was no significant change in Na iothalamate space or cumulative Na balance when ANG II infusion was continued for 6 days. Mean arterial pressure (MAP) rose from 100 +/- 3 to 132 +/- 2 mmHg after 3 days and remained near that level for the next 5 days of ANG II infusion. When RAP was prevented from rising with a servo-controlled aortic occluder, UNaV remained below control even after 6 days of ANG II infusion, cumulative Na balance increased by 210 +/- 37 meq, and Na iothalamate space rose by 1,158 +/- 244 ml. MAP did not plateau when RAP was servo-controlled during ANG II infusion but continued to rise and after 6 days averaged 157 +/- 3 mmHg. In three of the eight dogs in which RAP was servo-controlled during ANG II infusion, Na and water retention became so severe that MAP increased to 165-180 mmHg and pulmonary edema developed within 4-6 days. These data suggest that a rise in RAP is essential in allowing the kidneys to escape from the chronic Na-retaining actions of ANG II and in attaining Na balance and a stable level of MAP without severe volume expansion.

The present study was designed to quantitate the role of the renin-angiotensin system (RAS) in determining the chronic relationships between arterial pressure (AP), renal hemodynamics, and Na excretion. In six control dogs, Na balance was achieved during chronic step increases in Na intake from 5 to 500 meq/day with small increases in AP (<7 mmHg), moderate increases in GFR (19%), and decreases in filtration fraction (FF) and plasma renin activity. Similar increases in Na intake in six dogs with angiotensin II (AII) fixed, due to constant intravenous infusion of 5 ng . kg-1 . min-1 AII, caused large increases in AP (42%), GFR (31%) FF, and calculated renal Na reabsorption (TNa) above control. In six dogs with AII formation blocked with SQ 14,225, Na balance at intakes of 5-80 meq/day occurred at reduced AP, GFR, FF, and TNa, although plasma aldosterone concentration (PAC) was not substantially different from that in control dogs. At Na intakes above 240 meq/day, AP was not altered by SQ 14,225. These data indicate that during chronic changes in Na intake the RAS plays a major role, independent of changes in PAC, in allowing Na balance without large changes in GFR or AP. The mechanism whereby AII conserves Na chronically is through increased TNa, since steady-state TNa was increased by AII and decreased by SQ 14,225.

The interaction of angiotensin II and plasma K concentration in stimulating aldosterone secretion was studied in a group of six dogs by determining the aldosterone response to three levels of angiotensin II while the dogs were maintained on three levels of K intake. The levels of angiotensin were 1) the endogenous level, 2) the concentration resulting from infusion of 5 ng X kg-1 X min-1, and 3) the concentration resulting from infusion of 10 ng X kg-1 X min-1. Each level was maintained for 5 days. The three rates of K intake were 10, 100, and 200 meq/day, each maintained for 3 wk. Data were analyzed from days 1, 2, and 5 of the angiotensin infusion periods. The regressions obtained from plotting plasma K (PK) versus aldosterone concentration on day 5 of each level of infusion were 1) for no infusion (endogenous PRA = 0.4 to 0.5 ng ANG I X ml-1 X h-1), aldosterone = 5.04 X PK - 16.56; 2) for 5 ng X kg-1 X min-1 infusion, aldosterone = 12.20 X PK - 39.09; and 3) for 10 ng X kg-1 X min-1 infusion, aldosterone = 35.50 X Pk - 119.31. Each regression was significantly different (P less than 0.001) from the other two. The plasma K axis intercepts, which are the points at which aldosterone secretion is zero, were 3.29, 3.20, and 3.36 for the regression from the 0, 5, and 10 ng X kg-1 X min-1 infusion rates, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of this study was to ascertain the quantitative importance of glucagon in mediating protein-induced increases in renal blood flow (RBF) and glomerular filtration rate (GFR) during the postprandial state. Six chronically instrumented conscious dogs were each subjected to four protocols: normal protein control meal (C); high protein meat meal (M); somatostatin infusion and meat (S + M); and glucagon infusion. C produced small increases in RBF (12 +/- 2%) and GFR (14 +/- 2%) without changing arterial plasma glucagon. M produced marked increases in RBF (38 +/- 4%), GFR (41 +/- 5%), and glucagon (from 23.3 +/- 3.6 to 73.3 +/- 7.1 pg/ml) over a 3-h period. During S + M, RBF and GFR failed to increase while glucagon was suppressed by 36 +/- 8% over a 2-h period. When S was stopped, glucagon rose to 100 +/- 13.9 pg/ml over the next hour, yet RBF and GFR increased by only 14 +/- 4 and 10 +/- 3%, respectively. Glucagon infusion (3 ng X kg-1 X min-1, i.v.) markedly elevated plasma glucagon to 131.6 +/- 27.3 pg/ml, yet neither RBF nor GFR significantly changed. These data indicate that while a protein-rich meat meal does elevate arterial plasma glucagon, the rise is not great enough to elicit significant changes in renal hemodynamics. Thus, elevated plasma levels of glucagon cannot account for protein-mediated increases in RBF and GFR during the postprandial state.

1. This study was designed to quantify the role of angiotensin II in determining the chronic relationships between arterial pressure, renal haemodynamics and sodium excretion. 2. In six control dogs sodium balance was achieved during chronic increases in sodium intake from 5 to 495 mmol/day with small increases in arterial pressure (7mmHg), moderate increases in glomerular filtration rate (19%) and decreases in filtration fraction. Similar increases in sodium intake in dogs whose circulating levels of angiotensin II were fixed, due to a constant intravenous infusion of 4.85 pmol of angiotensin II min-1 kg-1, caused large increases in arterial pressure (42%), glomerular filtration rate (31%), filtration fraction and calculated renal sodium reabsorption above control. In six dogs whose angiotensin II formation was blocked by SQ 14 225, sodium balance at intakes of 5-80 mmol/day occurred at reduced arterial pressure, glomerular filtration rate, filtration fraction and sodium reabsorption although plasma aldosterone concentration was not substantially different from that in control dogs. At sodium intakes above 240 mmoL/day arterial pressure was not altered by SQ 14 225. 3. These data indicate that during chronic variations in sodium intake angiotensin II plays a major role, independently of changes in plasma aldosterone concentration, in allowing sodium balance without large fluctuations in glomerular filtration rate or arterial pressure. The mechanism whereby angiotensin II conserves sodium chronically is through increased sodium reabsorption, since steady-state sodium reabsorption was increased by angiotensin II and decreased by SQ 14 225.