Cardiovascular and renal action of platelet-activating factor in anesthetized dogs

S Vemulapalli, P J Chiu, A Barnett
1984 Hypertension  
Platelet-activating factor (PAF) has hypotensive effects similar to those of antihypertensive polar renomedullary lipid (APRL), a potent endogenous hypotensive lipid. In this study the cardiovascular and renal effects of PAF were characterized in anesthetized dogs. Intravenous infusion of PAF at 0.1 ^g/kg/mjn for 1 hour caused marked reduction in arterial blood pressure and cardiac output and was accompanied by minimal changes in heart rate. Concomitantly, renal blood flow, glomerular
more » ... rate, urine flow, and fractional excretion of Na+ and K+ fell significantly. Plasma renin activity was greatly stimulated (11.9 ± 1.66 vs 3.26 ± 0.45 ng/angiotensin I/ml/hr for the placebo group). There were no significant alterations in any of these parameters following PAF at a lower dose (0.03 /xg/kg/min for 1 hour). In a separate study, PAF at 0.1 /xg/kg/min for 20 minutes produced a decrease in left ventricular myocardial contractile force, concomitant with bradycardia and hypotension, which indicated the presence of a negative inotropic activity. It is concluded that systemic administration of PAF has a deleterious effect on kidney function due to arterial hypotension and diminished cardiac output. (Hypertension 6: 489-493, 1984) KEY WORDS • platelet-activating factor • ant (hypertensive polar renomedullary lipid • blood pressure • cardiac output • myocardial contractility • renal blood flow • glomerular filtration rate P LATELET-activating factor (PAF, PAFacether), a glycerophospholipid released from stimulated basophils, macrophages, and platelets, is considered an important mediator of inflammatory and allergic reactions. '~3 The chemical structure of PAF has been identified as l-0-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (alkyl ether analogs of phosphatidylcholine, AEPC), which is similar in hypotensive effect to that of antihypertensive polar remedullary lipid (APRL). 4 " 6 APRL and antihypertensive neutral renomedullary lipid (ANRL) are potent endogenous hypotensive lipids isolated from renal medulla. PAF, APRL, or ANRL, in microgram doses, lowered arterial pressure in guinea pigs, rats, and rabbits in the normal and hypertensive state following intravenous, 7 " 10 intramuscular, or oral administrations."" 13 We first reported that PAF infusion significantly reduced myocardial performance and renal function in anesthetized dogs. 14 Recently, it was demonstrated that intravenous administration of bolus doses (5-20 /xg/kg) of PAF to anesthetized dogs caused marked reductions in blood pressure (BP), heart rate (HR), cardiac output (CO), left ventricle (LV) dp/dt, blood
doi:10.1161/01.hyp.6.4.489 pmid:6378787 fatcat:ipggfeq4p5g4zbongrn2aynjfy