L-platelet activating factor induces changes on renal vascular resistance, vascular reactivity, and renin release in the isolated perfused rat kidney.
Rat kidneys were isolated and perfused with a modified Krebs-Henseleit buffer containing 4% albumin. Perfusate recirculated except during L-platelet activating factor (L-PAF), angiotensin II (ang II), and norepinephrine (NE) infusions. L-PAF caused a dose-dependent decrease in renovascular resistance (RVR): -6 +/- 3% at 10(-9)M, -12 +/- 6% at 10(-8)M, -18 +/- 3% at 10(-7) and -20 +/- 7% at 10(-6)M. L-PAF increased immunoreactive PGE (iPGE) and thromboxane (iTXB) release into the venous effluent from 2.4 +/- 0.2 to 3.9 +/- 0.4 ng/min (p less than 0.05) and from 2.1 +/- 0.4 to 3.5 +/- 0.5 ng/min (p less than 0.05), respectively. Vasodilation by L-PAF (10(-7) M) in the presence of indomethacin (INDO) (5 microM) was enhanced compared to the non-INDO response (RVR change: L-PAF = -18 +/- 3% vs. L-PAF = -26 +/- 3%; p less than 0.05). As a control for specificity, the was infused at 10(-9) M, 10(-8) M, and 10(-7) M. None of these concentrations changed renal vascular resistance. To study the vascular receptor responsible for L-PAF-induced vasodilation, dose-response curves to NE and ang II were established with and without L-PAF (10(-7) M). The NE dose-response curve was unchanged by L-PAF, whereas the ang II dose-response curve was shifted to the right by one order of magnitude. In kidneys pretreated with INDO (5 microM), the L-PAF-induced shift of the ang II dose-response relation was increased to 2-3 orders of magnitude.(ABSTRACT TRUNCATED AT 250 WORDS)
Schwertschlag
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Scherf
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Gerber
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JG
Mathias
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Nies
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D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D010972:Platelet Activating Factor / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects*; D012083:Renin / Q000378:metabolism*; D014655:Vascular Resistance / Q000187:drug effects*; D014664:Vasodilation
D010972:Platelet Activating Factor; D000804:Angiotensin II; D012083:Renin; D009638:Norepinephrine