title: Macula densa stimulation of renin is reversed by selective inhibition of neuronal nitric oxide synthase.
abstract: The neuronal isoform of nitric oxide synthase (nNOS) exists in the renal cortex predominantly in the macula densa, suggesting that nitric oxide (NO) derived from the macula densa plays a role in feedback regulation of renin in response to altered sodium metabolism. To determine if nNOS is a critical component in renin stimulation induced by dietary sodium restriction, rats received either normal sodium or a sodium-restricted diet (0.03%) for 7 days and subsequently were or were not treated with the selective inhibitor of nNOS 7-nitroindazole (7-NI) either acutely (50 mg/kg body wt ip) on the final day or chronically (20 mg/kg body wt ip 2 x/day) over the final 5 days. On the last day, rats were anesthetized with Inactin and fitted with arterial and renal venous catheters to collect blood and monitor blood pressure (BP) and a flow probe to measure renal blood flow (RBF). BP (105 vs. 108 mmHg) was similar in normal and low-sodium dietary groups, respectively, whereas RBF tended to be higher in the sodium-restricted group (6.5 +/- 0.3 vs. 7.6 +/- 0.4 ml.min-1.g kidney wt-1). Both renal venous renin (RR) and renin secretion rate (RSR) were elevated approximately fourfold by sodium restriction [RR = 5.8 +/- 0.8 vs. 20.5 +/- 2.7 ng angiotensin (ANG) I.ml-1.h-1; P < 0.001; RSR = 3.0 +/- 0.9 vs. 13.1 +/- 4.1 ng ANG I.h-1.min-1; P < 0.025]. Acute 7-NI did not change BP, RR, or RSR, but reduced RBF in sodium-restricted rats by 8% (P < 0.05). Chronic 7-NI had no effect on renin in rats on a normal diet, but reduced RR by one-half in the sodium-restricted group (to 9.9 +/- 1.6 ng ANG I-ml-1.h-1; P < 0.001) and reduced RSR to normal (diet) levels (to 3.9 +/- 1.4 ng ANG I.h-1.min-1; P < 0.05). Although selective NOS inhibition by 7-NI did not affect BP, RBF, or renin in control rats on a normal diet, chronic 7-NI reversed the stimulation of renin induced by dietary sodium restriction. These data suggest that nNOS-derived NO plays an important role in the macula densa during feedback stimulation of renin induced by dietary sodium restriction.
authors.affiliation: Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Michigan 48202, USA.
authors.forename: W H
authors.initials: WH
authors.lastname: Beierwaltes
mesh_terms: D000818:Animals; D004039:Diet, Sodium-Restricted; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007668:Kidney / Q000201:enzymology* / Q000502:physiology; D007672:Kidney Cortex / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D007191:Indazoles; D007527:Isoenzymes; D019001:Nitric Oxide Synthase; D012083:Renin; C080122:7-nitroindazole