title: Sympathetic stimulation of renin is independent of direct regulation by renal nitric oxide.
abstract: Nitric oxide (NO) regulates renin secretion through various pathways. The possibility that renal neuronal nitric synthase (nNOS) may mediate beta-adrenergic control of renin was tested. In six Inactin-anesthetized rats, renin secretion rate (RSR) was measured in response to the beta-agonist isoproterenol with and without selective inhibition of nNOS using 7-nitroindazole (7-NI, 50 mg/kg body weight [BW]). 7-NI had no effect on blood pressure (BP) or renal hemodynamics, while isoproterenol increased RSR by 9 ng AngI/h/min (P<.05) similarly with or without 7-NI. Isoproterenol decreased BP by 20 mm Hg (P<.001), but this depressor response was completely blocked by 7-NI. When acute endogenous stimulation of renal sympathetic nerve activity (RSNA) was induced by bilateral carotid occlusion, BP in 12 rats (105+/-5 mm Hg) rose transiently to peak at 121+/-6 mm Hg (P<.005) within 5 min, returning to baseline within 10 min. RSR rose threefold (2.1+/-0.5 to 7.6+/-3.3 ng AngI/ml/min/g kidney weight [KW]; P<.05). Next, 7-NI had no effect on BP (108+/-5 mm Hg), but subsequent carotid occlusion increased and sustained BP by 27+/-5 mm Hg (P<.001), but RSR did not change (2.46+/-0.94 ng AngI/ml/min/g KW). However, if after 7-NI treatment followed by carotid occlusion, the renal perfusion pressure was not allowed to rise, but held constant at 111+/-3 mm Hg, RSR increased from 3.03+/-0.79 to 12.97+/-3.41 ng AngI/ml/min/g KW (P<.025). Thus, neither beta-adrenergic stimulation of RSR with isoproterenol nor direct stimulation of RSR by activation of RSNA with carotid occlusion was modified by selective nNOS inhibition. These data suggest an important nNOS component in the regulation of BP in response to carotid occlusion, but do not support a direct role of renal nNOS mediating sympathetic regulation of RSR.
authors.affiliation: Hypertension and Vascular Research Division, Henry Ford Hospital and Health Sciences Center, Case Western Reserve University, Detroit Medical Campus, 2799 West Grand Boulevard, MI 48202-2689, USA. wbeierw1@hfhs.org
authors.forename: William H
authors.initials: WH
authors.lastname: Beierwaltes
mesh_terms: D000320:Adrenergic Fibers / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000502:physiology; D052248:Nitric Oxide Synthase Type I; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D012083:Renin / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D011943:Receptors, Adrenergic, beta; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D012083:Renin; D007545:Isoproterenol