The adrenergic system and the cardiovascular effects of platelet activating factor (1-0-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine) in SHR and WKY rats.
1-0-Hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (1-hexadecyl-2-acetyl-GPC, platelet activating factor, PAF) was previously shown to produce profound hypotension and sympathetic activation in conscious rats. To determine the role of the sympatho-adrenomedullary system in the cardiovascular responses elicited by 1-hexadecyl-2-acetyl-GPC, the vasoactive phospholipid was administered (1 nmol per 300 g) to a) intact, b) bilaterally demedullated, and c) propranolol- (a beta-adrenoceptor blocker) treated SHR and WKY rats. The hypotensive response to 1-hexadecyl-2-acetyl-GPC was prolonged in demedullated or propranolol-pretreated WKY rats and in propranolol-treated SHR rats. The extreme tachycardia produced by 1-hexadecyl-2-acetyl-GPC in both the WKY and SHR rats was abolished by propranolol pretreatment. Pressor responses to norepinephrine during the 1-hexadecyl-2-acetyl-GPC-induced hypotension in propranolol-pretreated rats were suppressed in both the normotensive and SHR rats. Plasma acetylhydrolase activity, which inactivates PAF, was higher in hypertensive (SHR) rats or demedullated WKY rats than in the normotensive (WKY) rats. These results show that the tachycardia evoked by 1-hexadecyl-2-acetyl-GPC is mediated solely by sympathetic activation and the beta-adrenergic receptors and further indicate the major role of the sympathetic system and beta-adrenoceptors in recuperation from 1-hexadecyl-2-acetyl-GPC-induced shock. The data also suggest that acetylhydrolase in serum is an important regulatory enzyme for controlling PAF levels in the vascular compartment.
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010741:Phospholipases A / Q000097:blood; D010972:Platelet Activating Factor / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects*
D010972:Platelet Activating Factor; D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D009638:Norepinephrine