Neuronal nitric oxide synthase modulates rat renal microvascular function.
This study was performed to determine the influence of neuronal nitric oxide synthase (nNOS) on renal arteriolar tone under conditions of normal, interrupted, and increased volume delivery to the macula densa segment and on the microvascular responses to angiotensin II (ANG II). Experiments were performed in vitro on afferent (21.2 +/- 0.2 microns) and efferent (18.5 +/- 0.2 microns) arterioles of kidneys harvested from male Sprague-Dawley rats, using the blood-perfused juxtamedullary nephron technique. Superfusion with the specific nNOS inhibitor, S-methyl-L-thiocitrulline (L-SMTC), decreased afferent and efferent arteriolar diameters, and these decreases in arteriolar diameters were prevented by interruption of distal volume delivery by papillectomy. When 10 mM acetazolamide was added to the blood perfusate to increase volume delivery to the macula densa segment, afferent arteriolar vasoconstrictor responses to L-SMTC were enhanced, but this effect was again completely prevented after papillectomy. In contrast, the arteriolar diameter responses to the nonselective NOS inhibitor, N omega-nitro-L-arginine (L-NNA) were only attenuated by papillectomy. L-SMTC (10 microM) enhanced the efferent arteriolar vasoconstrictor response to ANG II but did not alter the afferent arteriolar vasoconstrictor responsiveness to ANG II. In contrast, L-NNA (100 microM) enhanced both afferent and efferent arteriolar vasoconstrictor responses to ANG II. These results indicate that the modulating influence of nNOS on afferent arteriolar tone of juxtamedullary nephrons is dependent on distal tubular fluid flow. Furthermore, nNOS exerts a differential modulatory action on the juxtamedullary micro-vasculature by enhancing efferent, but not afferent, arteriolar responsiveness to ANG II.
Ichihara
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Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana 70112-2699, USA.
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D000086:Acetazolamide / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000502:physiology*; D002956:Citrulline / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply*; D007686:Kidney Tubules, Distal / Q000098:blood supply / Q000294:innervation; D008297:Male; D008833:Microcirculation; D009474:Neurons / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014666:Vasomotor System / Q000502:physiology; D014741:Video Recording
D004791:Enzyme Inhibitors; D000804:Angiotensin II; D002956:Citrulline; D019001:Nitric Oxide Synthase; D013890:Thiourea; C086717:S-methylthiocitrulline; D000109:Acetylcholine; D000086:Acetazolamide