Nitric oxide modulates sympathoexcitatory cardiac-cardiovascular reflexes elicited by bradykinin.
A number of studies have demonstrated an important role for nitric oxide (NO) in central and peripheral neural modulation of sympathetic activity. To assess the interaction and integrative effects of NO release and sympathetic reflex actions, we investigated the influence of inhibition of NO on cardiac-cardiovascular reflexes. In anesthetized, sinoaortic-denervated and vagotomized cats, transient reflex increases in arterial blood pressure (BP) were induced by application of bradykinin (BK, 0.1-10 microg/ml) to the epicardial surface of the heart. The nonspecific NO synthase (NOS) inhibitor NG-monomethyl-L-arginine (L-NMMA, 10 mg/kg iv) was then administered and stimulation was repeated. L-NMMA increased baseline mean arterial pressure (MAP) from 129 +/- 8 to 152 +/- 9 mmHg and enhanced the change in MAP in response to BK from 32 +/- 3 to 39 +/- 5 mmHg (n = 9, P < 0.05). Pulse pressure was significantly enhanced during the reflex response from 6 +/- 4 to 27 +/- 6 mmHg after L-NMMA injection due to relatively greater potentiation of the rise in systolic BP. Both the increase in baseline BP and the enhanced pressor reflex were reversed by L-arginine (30 mg/kg iv). Because L-NMMA can inhibit both brain and endothelial NOS, the effects of 7-nitroindazole (7-NI, 25 mg/kg ip), a selective brain NOS inhibitor, on the BK-induced cardiac-cardiovascular pressor reflex also were examined. In contrast to L-NMMA, we observed significant reduction of the pressor response to BK from 37 +/- 5 to 18 +/- 3 mmHg 30 min after the administration of 7-NI (n = 9, P < 0.05), an effect that was reversed by L-arginine (300 mg/kg iv, n = 7). In a vehicle control group for 7-NI (10 ml of peanut oil ip), the pressor response to BK remained unchanged (n = 6, P > 0.05). In conclusion, neuronal NOS facilitates, whereas endothelial NOS modulates, the excitatory cardiovascular reflex elicited by chemical stimulation of sympathetic cardiac afferents.
Tjen-A-Looi
S C
SC
Department of Medicine, University of California, Irvine, California 92697-4075, USA. stjenalo@uci.edu
Phan
N T
NT
Longhurst
J C
JC
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure; D001920:Bradykinin / Q000494:pharmacology*; D002415:Cats; D003714:Denervation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006339:Heart Rate; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D013564:Sympathetic Nervous System / Q000378:metabolism*; D014628:Vagotomy; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007191:Indazoles; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D001920:Bradykinin; C080122:7-nitroindazole