Inhibition of nitric oxide synthesis extends cerebrovascular autoregulation during hypertension.
In anesthetized intact rats, cerebral blood flow is autoregulated until mean arterial blood pressure (MAP) exceeds 150 mmHg. At higher pressures cerebral blood flow breaks through autoregulation and rapidly increases. However, interruption of the arterial baroreceptor reflex eliminates breakthrough of autoregulation. Thus, breakthrough may reflect active rather than passive vasodilatation. We, therefore, sought to determine if breakthrough depends upon synthesis of the vasodilator nitric oxide. Thirty-eight anesthetized adult male Sprague-Dawley rats were studied. In all, MAP was raised by slow i.v. infusion of phenylephrine. In rats pretreated with the nitric oxide synthase inhibitor L-nitroarginine (L-NA; 22 mg/kg i.v.) or with a combination of L-NA plus D-arginine (D-Arg; 240 mg/kg i.v.), breakthrough did not occur even when MAP exceeded 185 mmHg (L-NA) and 165 mmHg (D-Arg). In contrast, breakthrough occurred in rats treated with L-NA plus L-arginine (L-Arg; 240 mg/kg i.v.) and in rats whose basal vascular tone had been increased by pretreatment with arginine vasopressin prior to infusion of phenylephrine. Removal of sympathetic innervation to cerebral vessels attenuated, but did not eliminate, effects of L-NA on breakthrough. Thus, vasodilatation seen with breakthrough of autoregulation depends upon release of nitric oxide or a nitric oxide donor.
Talman
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Department of Neurology, University of Iowa College of Medicine, Iowa City 52242, USA.
Dragon
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DN
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D019335:Nitroarginine; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction
D001127:Arginine Vasopressin; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine