Renal vascular reactivity to vasodilator prostaglandins in genetically hypertensive rats.
The objective of this study was to test the hypothesis that the vasodilator prostaglandins E2 (PGE2) and PGI2) participate in the mechanisms involved in the increased renal vascular reactivity (RVR) observed in genetic hypertension. Studies were performed on anesthetized young and adult spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY). Renal blood flow (RBF) was measured during bolus injections into the renal artery of different doses of viprostol and iloprost (stable receptor agonists of PGE2 and PGI2, respectively) before and during inhibition of prostaglandin synthesis by indomethacin. Under control conditions, PGE2 increased RBF equally in young SHR and WKY. However, after cyclooxygenase inhibition the PGE2-induced increase in RBF was larger in young SHR than in WKY. Adult SHR displayed reduced reactivity to PGE2 relative to age-matched WKY under control conditions. This strain difference was abolished after indomethacin administration. PGI2 increased RBF slightly in young rats before and after indomethacin administration. In contrast, both strains of older animals displayed significant increases in RBF in response to PGI2 injections. Indomethacin administration enhanced this PGI2-induced relaxation in adult SHR but not WKY. We propose that the action of vasodilator PGs in the renal vasculature of rats developing hypertension may be limited by low density of their renal receptors and/or the opposing action of vasoconstrictor PGs. As age advances, PGI2 seems to be activated, possibly as part of a regulatory response to counterbalance the increased renal vascular resistance following the establishment of the disease.
Chatziantoniou
C
C
Department of Physiology, University of North Carolina, Chapel Hill 27599-7545.
Arendshorst
W J
WJ
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011921:Rats, Inbred WKY; D012044:Regression Analysis; D012079:Renal Circulation / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D014665:Vasodilator Agents; D007213:Indomethacin