Antagonism of the vasodilator effects of a platelet activating factor precursor in anesthetized spontaneously hypertensive rats.
The hemodynamic effects of platelet activating factor (PAF), PAF antagonists and a precursor of PAF, 1-palmityl-2-acetyl-glycerol (PAG), were examined in pentobarbital-anesthetized spontaneously hypertensive rats to determine whether functionally significant amounts of PAF are produced via the cholinephosphotransferase pathway of PAF synthesis in vivo. Intravenous bolus doses of PAF, PAG and nitroprusside elicited hypotension and active mesenteric vasodilatation. Responses to PAG were slower in onset and longer in duration than those of PAF and nitroprusside. The specific PAF antagonists, CV-3988 and SRI 63-675, attenuated PAG- and PAF-, but not nitroprusside-induced changes in blood pressure and mesenteric flow/resistance. In contrast, captopril, which blocked the effects of angiotensin I, did not influence the hypotension caused by PAG, PAF and nitroprusside. The results suggest that the vasodilator effects of PAG are attributable to PAF produced from this alkylacetylglycerol, and the renin-angiotensin system does not appear to influence the biotransformation of PAG to PAF or the hypotensive action of PAF.
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Department of Pharmacology, Medical School, University of Minnesota, Minneapolis 55455.
Dunham
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D000818:Animals; D002216:Captopril / Q000494:pharmacology; D002798:Diacylglycerol Cholinephosphotransferase / Q000502:physiology; D005995:Glyceryl Ethers / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010742:Phospholipid Ethers / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000096:biosynthesis* / Q000502:physiology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D014665:Vasodilator Agents / Q000494:pharmacology*
D005995:Glyceryl Ethers; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D011804:Quinolines; D014665:Vasodilator Agents; C053130:SRI 63-675; D009599:Nitroprusside; C037913:CV 3988; C055394:1-palmityl-2-acetylglycerol; D002216:Captopril; D002798:Diacylglycerol Cholinephosphotransferase