Role of endogenous centrally released NO in cardiovascular adaptation to hypovolemia in WKY and SHR.
The role of endogenous centrally released nitric oxide (NO) during hypovolemia was investigated in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Bleeding of the rats (1.3% of blood volume) was performed after intracerebroventricular (ICV) administration of: 1) artificial cerebrospinal fluid (series 1, time control, 8 WKY and 8 SHR); 2) 0.5 mg NG-nitro-L-arginine (L-NNA, 2.3 nmol), an inhibitor of NO synthesis (series 2, 8 WKY and 7 SHR); and 3) 0.5 mg L-NNA followed by 1 mg (5.8 nmol) of L-arginine (L-Arg) (6 WKY and 5 SHR). In WKY, hypotension was associated with significant bradycardia (P < 0.001), whereas in SHR slight acceleration of heart rate was observed. In series 2 hemorrhage resulted in a small but significant increase of mean arterial pressure (MAP; P < 0.05) and considerable tachycardia (P < 0.001). In SHR, L-NNA did not modify the decrease of MAP during hypovolomia, and bleeding resulted in a significant bradycardia (P < 0.001). Pretreatment with L-Arg in series 3 was able to reverse the effects of L-NNA on changes of MAP and heart rate during hypovolemia. The results indicate that the central nitroxidergic system plays a significant role in eliciting hypotension and bradycardia in normotensive WKY during hemorrhage. Function of the central nitroxidergic system is significantly altered in SHR in which NO appears to prevent hemorrhagic bradycardia and to reduce the hypotensive effect.
Paczwa
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Department of Clinical and Applied Physiology, Warsaw Medical Academy, Poland.
Budzikowski
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Szczepańska-Sadowska
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D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001810:Blood Volume; D006339:Heart Rate / Q000187:drug effects; D007276:Injections, Intraventricular; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011921:Rats, Inbred WKY / Q000502:physiology*
D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine