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A study was conducted to analyze the influence of chronic angiotensin converting enzyme deficiency on the magnitude of tubuloglomerular feedback responses. The genotype was determined by polymerase chain reaction on DNA obtained from the tail. Results indicated that angiotensin II is an important component in the signal transmission pathway that connects the macula densa with the glomerular vascular pole.

The effect of the adenosine type 1 receptor agonist N(super 6)-cyclohexyladenosine (CHA) on glomerular vascular reactivity in angiotensin II type 1A receptor-deficient mice was investigated. Experimental results showed the inhibition of adenosine-1 receptor-mediated preglomerular vasoconstriction in male angiotensin II type 1A receptor knockout mice. It was also found that the decrease in stop-flow pressure after local administration of CHA is significantly affected in the receptor-deficient mice.

To investigate the role of aquaporin-1 (AQP1) water channels in proximal tubule function, in vitro proximal tubule microperfusion and in vivo micropuncture measurements were done on AQP1 knockout mice. The knockout mice were generated by targeted gene disruption and found previously to be unable to concentrate their urine in response to water deprivation. Unanesthetized knockout mice consumed 2.8-fold more fluid than wild-type mice and had lower urine osmolality (505 [+ or -] 40 vs. 1081 [+ or -] 68 milliosmolar). Transepithelial osmotic water permeability ([P.sub.f]) in isolated microperfused S2 segments of proximal tubule from AQP1 knockout [-/-] mice was 0.033 [+ or -] 0.005 cm/s (SE, n = 6 mice, 37 [degrees] C), much lower than that of 0.15 [+ or -] 0.03 cm/s (n = 8) in tubules from wild-type [+/+] mice (P < 0.01). In the presence of isosmolar luminal perfusate and bath solutions, spontaneous fluid absorption rates (nl/min/mm tubule length) were 0.31 [+ or -] 0.12 (-/-, n = 5) and 0.64 [+ or -] 0.15 (+/+, n = 8). As determined by free-flow micropuncture, the ratios of tubular fluid-to-plasma concentrations of an impermeant marker TF/P in end proximal tubule fluid were 1.36 [+ or -] 0.05 (-/-, n = 8 mice [53 tubules]) and 1.95 [+ or -] 0.09 (+/+, n = 7 mice [40 tubules]) (P < 0.001), corresponding to 26 [+ or -] 3% [-/-] and 48 [+ or -] 2% [+/+] absorption of the filtered fluid load. In collections of distal tubule fluid, TF/P were 2.8 [+ or -] 0.3 [-/-] and 4.4 [+ or -] 0.5 [+/+], corresponding to 62 [+ or -] 4% [-/-] and 76 [+ or -] 3% [+/+] absorption (P < 0.02). These data indicate that AQP1 deletion in mice results in decreased transepithelial proximal tubule water permeability and defective fluid absorption. Thus, the high water permeability in proximal tubule of wild-type mice is primarily transcellular, mediated by AQP1 water channels, and required for efficient near-isosmolar fluid absorption.

An analysis of the absence of the tobuloglomerular feedback (TGF) responses in AT1A receptor-deficient mice was presented. The study utilized TGF responses in a strain of mice that carries a null mutation in the angiotensin II AT1A receptor gene. Results of the analysis revealed that AT1A receptor-mediated effects of angiotensin II are significant components of TGF responsiveness.

A study of neuroregulation of electrolyte transport in the porcine distal colon using electrical transmural stimulation (ETS) shows that cholinergic submucosal neurons regulate epithelial ion transport in the porcine distal colon and neuropeptide Y(NPY) inhibits neural activity of leukotriene-sensitive neurons in the colon. ETS of the colonic mucosa submucosa incubated on Ussing chamber enhances short-circuit current indicating that part of response is mediated by Cl secretion.

Lorenz, John N., Patrick J. Schultheis, Timothy Traynor, Gary E. Shull, and Jurgen Schnermann. Micropuncture analysis of single-nephron function in NHE3-deficient mice. Am. J. Physiol. 277 (Renal Physiol. 46): F447-F453, 1999.--The Na/H exchanger isoform 3 (NHE3) is expressed in the proximal tubule and thick ascending limb and contributes to the reabsorption of fluid and electrolytes in these segments. The contribution of NHE3 to fluid reabsorption was assessed by micropuncture in homozygous ([Nhe3.sup.-/-]) and heterozygous ([Nhe3.sub.+/-]) knockout mice, and in their wild-type (WT, [Nhe3.sup.+/+]) littermates. Arterial pressure was lower in the [Nhe3.sup.-/-] mice (89 [+ or -] 6 mmHg) compared with [Nhe3.sup.+/+] (118 [+ or -] 4) and [Nhe3.sup.+/-] (108 [+ or -] 5). Collections from proximal and distal tubules demonstrated that proximal fluid reabsorption was blunted in both [Nhe3.sup.+/-] and [Nhe3.sup.-/-] mice (WT, 4.2 [+ or -] 0.3; [Nhe3.sup.+/-], 3.4 [+ or -] 0.2; and [Nhe3.sup.-/-], 2.6 [+ or -] 0.3 nl/min; P [is less than] 0.05). However, distal delivery of fluid was not different among the three groups of mice (WT, 3.3 [+ or -] 0.4 nl/min; [Nhe3.sup.+/-], 3.3 [+ or -] 0.2 nl/min; and [Nhe3.sup.-/-], 3.0 [+ or -] 0.4 nl/min; P [is less than] 0.05). In [Nhe3.sup.-/-] mice, this compensation was largely attributable to decreased single-nephron glomerular filtration rate (SNGFR): 10.7 [+ or -] 0.9 nl/min in the [Nhe3.sup.+/+] vs. 6.6 [+ or -] 0.8 nl/min in the [Nhe3.sup.-/-], measured distally. Proximal-distal SNGFR differences in [Nhe3.sup.-/-] mice indicated that much of the decrease in SNGFR was due to activation of tubuloglomerular feedback (TGF), and measurements of stop-flow pressure confirmed that TGF is intact in [Nhe3.sup.-/-] animals. In contrast to [Nhe3.sup.-/-] mice, normalization of early distal flow rate in [Nhe3.sup.+/-] mice was not related to decreased SNGFR (9.9 [+ or -] 0.7 nl/min), but rather, to increased fluid reabsorption in the loop segment ([Nhe3.sup.+/+], 2.6 [+ or -] 0.2; [Nhe3.sup.+/-], 3.6 [+ or -] 0.5 nl/min). We conclude that NHE3 is a major Na/H exchanger isoform mediating [Na.sup.+] and fluid reabsorption in the proximal tubule. In animals with NHE3 deficiency, normalization of fluid delivery to the distal tubule is achieved through alterations in filtration rate and/or downstream transport processes. kidney; single-nephron glomerular filtration rate; sodium/ proton exchange; proximal tubule; tubuloglomerular feed-back