Nitric oxide mediates the inhibitory action of platelet-activating factor on angiotensin II-induced renal vasoconstriction, in vivo.
The objective of our study was to determine the mechanism(s) involved in the inhibitory effect of platelet-activating factor on renal vascular reactivity, in vivo. Bolus injections of vasoconstrictor agonists were administered into the renal circulation of pentobarbital anesthetized male Wistar rats at a dose to cause a transient 45 to 50% decrease in renal blood flow. Intrarenal infusion of platelet-activating factor (PAF) at 2.5 ng/min/kg attenuated the vasoconstrictor response to angiotensin II by 66%, a significantly smaller reduction of 35% for norepinephrine-mediated vasoconstriction, 22% for vasopressin-mediated vasoconstriction and no alteration of KCl-mediated vasoconstriction. The preferential inhibitory effect of platelet-activating factor on angiotensin II-mediated renal vasoconstriction was mimicked by the intrarenal infusion of either 0.2 to 5 micrograms/min/kg methacholine (endothelium-dependent vasodilator) or 2 micrograms/min/kg sodium nitroprusside (nitric oxide donor). After inhibition of nitric oxide synthesis with NG-monomethyl-L-arginine, intrarenal infusion of PAF or methacholine reduced angiotensin II-mediated renal vasoconstriction significantly less than that observed in the absence of NG-monomethyl-L-arginine. Therefore, this study provides evidence that the shared ability of platelet-activating factor and methacholine to selectively reduce angiotensin II-mediated renal vasoconstriction involves endothelium-derived nitric oxide.
Handa
R K
RK
Department of Physiology and Pharmacology, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina, USA.
Strandhoy
J W
JW
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects*; D016014:Linear Models; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects*; D019323:omega-N-Methylarginine
D004791:Enzyme Inhibitors; D010972:Platelet Activating Factor; D000804:Angiotensin II; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine