Transmission of arterial baroreflex signals depends on neuronal nitric oxide synthase.
Because inhibition of neuronal nitric oxide synthase in the nucleus tractus solitarii blocks cardiovascular responses to activation of local glutamate receptors, and because glutamate is a neurotransmitter of baroreceptor afferent nerves, we sought to test the hypothesis that neuronal nitric oxide synthase inhibition would block baroreflex transmission and cause hypertension. We determined reflex heart rate responses to intravenous phenylephrine and sodium nitroprusside in 5 anesthetized rats before and after bilateral microinjection (100 nL) of the neuronal nitric oxide synthase inhibitor AR-R 17477 (7.5 nmol) into the nucleus tractus solitarii. The inhibitor significantly increased mean arterial pressure without affecting heart rate, and it significantly reduced the gain of the baroreflex. After administration of the inhibitor, reflex responses of heart rate to changes in mean arterial pressure were always less than those responses to the same, or less, change in mean arterial pressure in the same animal without administration of the inhibitor. Microinjection of saline (100 nL) bilaterally into the nucleus tractus solitarii did not lead to hypertension or change baroreflex responses. These data support the hypothesis and suggest that neuronal nitric oxide synthase is critical to transmission of baroreflex signals through the nucleus tractus solitarii.
Department of Neurology, Laboratory of Neurobiology, VAMC and University of Iowa, Iowa City, IA 52242, USA. william-talman@uiowa.edu
William T
WT
Talman
Deidre Nitschke
DN
Dragon
D000578:Amidines / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D018698:Glutamic Acid / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D007267:Injections; D008297:Male; D009474:Neurons / Q000201:enzymology; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000502:physiology; D012021:Reflex, Abnormal / Q000187:drug effects; D015398:Signal Transduction; D017552:Solitary Nucleus / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects; D013876:Thiophenes / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*
D000578:Amidines; D004791:Enzyme Inhibitors; C486880:N-(4-(2-((3-chlorophenylmethyl)amino)ethyl)phenyl)-2-thiophenecarboxamide; D017470:Receptors, Glutamate; D013876:Thiophenes; D009599:Nitroprusside; D010656:Phenylephrine; D009569:Nitric Oxide; D018698:Glutamic Acid; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat