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Objective: To determine whether 6 weeks continuous treatment with an angiotensin converting enzyme (ACE) inhibitor reduced renal vascular responsiveness in vivo, since this treatment results in extensive phenotypic conversion of afferent arteriolar cells from contractile to endocrine-like, renin secretory cells., Methods: Enalapril (10 microg/kg per h s.c.) was delivered continuously for 6 weeks. In anaesthetized rabbits (treated or sham), arterial blood pressure and renal blood flow were measured and renal responsiveness tested by constructing dose-response curves to bolus doses of phenylephrine, angiotensin II and acetylcholine delivered directly into the renal artery., Results: ACE inhibition resulted in a significant shift to the left in the renal vascular conductance responses to acetylcholine (P < 0.005) and angiotensin II (P < 0.05), indicating enhanced, not reduced, responsiveness to these agents. There were no significant effects of chronic ACE inhibition on the conductance responses to phenylephrine., Conclusions: Contrary to our hypothesis, 6 weeks ACE inhibition did not reduce renal vascular responsiveness to three vasoactive agents, suggesting that the phenotypic changes observed in the afferent arterioles and to a lesser extent the interlobular arteries, were either insignificant or compensated for by other changes in renal circulatory control.

Objectives: We tested whether vasoconstriction of juxtamedullary glomerular arterioles contributes to vasopressin V1 -receptor-mediated reductions in medullary perfusion (MBF)., Design and Methods: The left kidney of pentobarbitone anaesthetized rabbits was denervated, a perivascular flow probe placed around the renal artery and laser-Doppler flow probes positioned in the inner medulla and on the cortical surface. Rabbits then received a 30 min intravenous infusion of [Phe2,Ile3,Orn8]vasopressin (V1 -AG; 30 ng/kg per min; n = 7) or its vehicle (n = 7). Kidneys were perfusion fixed at the final recorded mean arterial pressure (MAP) and filled with methacrylate casting material. Diameters of afferent and efferent arterioles were determined by scanning electron microscopy., Results: V1 -AG increased MAP (19 +/- 3%) and reduced MBF (30 +/- 8%) but not cortical perfusion or total renal blood flow. Vehicle-treatment did not significantly affect these variables. After vehicle- and V1-AG-treatment, juxtamedullary afferent arteriole luminal diameter averaged 15.35 +/- 1.31 and 15.88 +/- 1.86 microm, respectively (P= 0.92), while juxtamedullary efferent arteriole luminal diameter averaged 17.75 +/- 1.86 and 18.36 +/- 2.24 microm, respectively (P= 0.93)., Conclusions: V1-AG reduced MBF but did not significantly affect juxtamedullary arteriolar diameter. Our results therefore do not support a role for juxtamedullary arterioles in producing V1-receptor-mediated reductions in MBF, suggesting that downstream vascular elements (e.g. outer medullary descending vasa recta) might be involved.

Objective: To determine the effects on pre- and post-glomerular vascular resistance of adrenocorticotrophin (ACTH)-induced hypertension in rats, before and after blockade of nitric oxide formation., Design: Four groups of Sprague-Dawley rats were studied. Measurements were made in ACTH- (Synacthen Depot, 0.25 mg/kg twice daily for 8 days) and sham-treated anaesthetized rats, before and after either Nomega-nitro-L-arginine (L-NNA, 6 mg/kg) or vehicle., Methods: Whole-kidney and single-nephron haemodynamics and function were measured. Glomerular capillary pressure was estimated from tubular stop-flow pressure measurements., Results: Blood pressure (P < 0.001), renal blood flow (RBF, P < 0.05) and glomerular filtration rate (P < 0.01) were increased following ACTH treatment compared with sham. There were no differences in either total renal, or pre- or post-glomerular vascular resistances, but stop-flow-estimated glomerular capillary pressure was elevated (P < 0.001) as was single-nephron glomerular filtration rate (SNGFR) (P < 0.001) and single-nephron blood flow (P < 0.01 ) in the ACTH- compared to the sham-treated rats. L-NNA treatment increased blood pressure by a similar extent in both ACTH- and sham-treated rats, but reduced RBF (P < 0.05) and glomerular filtration rate (GFR) (P < 0.05) more in the ACTH group; similar changes were seen in single-nephron values. L-NNA increased pre- and post-glomerular resistances to a greater extent in the ACTH group., Conclusions: ACTH-induced hypertension produced glomerular hypertension and hyperfiltration, which may be due to nitric oxide-related vasodilatation of the renal vasculature.

The contribution of renal vascular conductance to the fall in total peripheral conductance during the development of renal wrap hypertension was determined in conscious rabbits. Measurements were made 28 days after renal wrap (n = 9) or sham operation (n = 8). Blood pressure was about 50 mmHg higher in the wrapped group as compared to the sham-operated group. This was due to a fall in total peripheral conductance of about 42%. Cardiac output was not significantly different between wrap and sham groups. Renal vascular conductance was 0.42 ml/min per mmHg lower in the wrap compared to the sham-operated group (P less than 0.001). Total peripheral conductance was 3.93 ml/min per mmHg lower in the wrap compared to the sham group (P less than 0.01). The reduction in renal vascular conductance in wrapped rabbits, which is probably due to compression caused by the thickening renal capsule, accounts for about 10% of the fall in total peripheral conductance. We suggest that this mechanically induced reduction in renal conductance is involved in the initiation and maintenance of the hypertension, but is only a minor contributor to the overall change in blood pressure.

Serial measurements of mean arterial pressure and glomerular filtration rate (GFR) were made in rabbits before and 10, 28 and 56 days after bilateral renal cellophane wrap (n = 8) or sham operation (n = 6). No significant changes were seen 10 days after renal wrap, but by 28 days GFR was reduced by 50 +/- 3% and mean arterial pressure had risen by 42 +/- 5 mmHg. No significant further changes occurred over the subsequent month. Changes in plasma renin activity after renal wrapping were not significantly different to those seen after sham operation. In a separate series of experiments, renal extraction ratio of para-aminohippurate (PAH), 28 days after renal wrap, averaged 63 +/- 4% (n = 6) compared to 83 +/- 2% (n = 5) after sham operation. Calculated renal blood flow of the hypertensive rabbits was only about 40% of that in the sham operated rabbits. Thus large reductions in GFR, renal blood flow and PAH extraction ratio occurred following bilateral renal wrapping and these changes may reflect compression of the kidney by the cellophane induced fibrous capsule. These reductions occurred concomitantly with the rise in arterial blood pressure.