Selective neuronal nitric oxide synthase inhibition blocks furosemide-stimulated renin secretion in vivo.
The macula densa is a regulatory site for renin. It contains exclusively the neuronal isoform of nitric oxide synthase (NOS), suggesting NO could stimulate renin secretion through the macula densa pathway. To test whether neuronal NOS mediates renin secretion, renin was stimulated by either the renal baroreceptor or the diuretic furosemide (acting through the macula densa pathway). Renin secretion rate (RSR) was measured in 12 Inactin-anesthetized rats at normal (104 +/- 3 mmHg) and reduced renal perfusion pressure (65 +/- 1 mmHg), before and after selective blockade of the neuronal NOS with 7-nitroindazole (7-NI, 50 mg/kg ip). 7-NI had no effect on basal blood pressure (102 +/- 2 mmHg) or renal blood flow (RBF). Decreasing renal perfusion pressure doubled RSR from 11.8 +/- 3.3 to 22.9 +/- 5.7 ng ANG I.h-1.min-1 (P < 0.01) (ANG I is angiotensin I). Similarly, in 7-NI-treated rats, reduced perfusion doubled RSR from 8.5 +/- 1.8 to 20.5 +/- 6.2 ng ANG I.h-1.min-1 (P < 0.01). Renal hemodynamics and RSR were measured in response to 5 mg/kg iv furosemide in 12 control rats and 11 rats treated with 7-NI. Blocking neuronal NOS did not alter blood pressure (102 +/- 2 mmHg), RBF (5.8 +/- 0.4 ml.min-1.g kidney wt-1), or renal vascular resistance (18.7 +/- 1.4 mmHg.ml-1.min.g kidney wt).(ABSTRACT TRUNCATED AT 250 WORDS)
Beierwaltes
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Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Michigan 48202, USA.
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology*; D007191:Indazoles / Q000494:pharmacology; D007668:Kidney / Q000294:innervation; D008297:Male; D009474:Neurons / Q000201:enzymology*; D019001:Nitric Oxide Synthase; D011311:Pressoreceptors / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000378:metabolism*; D000092502:Renin Inhibitors
D000594:Amino Acid Oxidoreductases; D004791:Enzyme Inhibitors; D005665:Furosemide; D007191:Indazoles; D019001:Nitric Oxide Synthase; D012083:Renin; D000092502:Renin Inhibitors; C080122:7-nitroindazole