Possible endothelial modulation of prostaglandin-stimulated renin release.
Studies were run to determine whether the renal microvascular endothelium influences renin release. Blood-free rat renal cortical slices were incubated in a bicarbonate buffer for 60 min and sampled at 30 and 60 min to determine renin concentration and at 60 min for prostaglandin (PG) E2 and I2 (6-keto-PGF1 alpha) synthesis. Stimulation by 10(-6) M melittin of endogenous PGs simultaneously increased renin release, PGE2, and PGI2 synthesis, and all were inhibited by 1.6 x 10(-6) M meclofenamate. Renin release was stimulated with isoproterenol [26.2 +/- 2.4 ng angiotensin I (ANG I) .h-1.mg-1.30 min-1; P less than 0.001], PGI2 (32.3 +/- 7.4 ng ANG I.h-1.mg-1.mg-1.30 min-1; P less than 0.005), and PGE2 (25.7 +/- 2.8 ng ANG I.h-1.mg-1.30 min-1, P less than 0.001). Acetylcholine did not affect basal renin but potentiated the response to PGE2 by 80% (46.0 +/- 5.8 ng ANG I.h-1.mg-1.30 min-1; P less than 0.001). Atropine (10(-7) M) reversed this potentiation. Deendothelialization of renal microvessels with H2O2 eliminated PGI2, but neither PGE2 nor renin release, and reversed acetylcholine-potentiation of PGE2-stimulated renin release as did meclofenamate. Hemoglobin increased PGE2-stimulated renin similarly to acetylcholine. These studies suggest that stimulating the endothelium with acetylcholine results in selective potentiation of PGE2-stimulated renin release, which may be mediated through some cyclooxygenase product and is independent of endothelium-derived relaxing factor. Thus the renal endothelium may influence or modulate renin release.
Beierwaltes
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Hypertension Research Division, Henry Ford Hospital, Detroit, Michigan 48202.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology*; D066298:In Vitro Techniques; D007672:Kidney Cortex; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D008555:Melitten / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation; D012083:Renin / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology
D011453:Prostaglandins; D014665:Vasodilator Agents; D008555:Melitten; D008469:Meclofenamic Acid; D012083:Renin; D000109:Acetylcholine