Role of the endothelium and cyclic GMP in renal vasodilator responses to cryptolepine in rats.
Isolated perfused rat kidney was used to examine the possible mechanisms involved in the hypotensive/vasodilator actions of cryptolepine. In kidneys preconstricted by phenylephrine (PE 5-7.5 x 10(-7) M), cryptolepine at bolus doses of 2.5, 5, and 10 micrograms elicited dose-dependent reductions in perfusion pressure by 29.8 +/- 4.1, 43.3 +/- 3.9, and 54.3 +/- 4.9 mm Hg, respectively. In the presence of indomethacin, cryptolepine-induced reduction in perfusion pressure was not significantly changed, suggesting a lack of a cyclooxygenase-mediated component in its renal vasodilator response. Removal of the endothelium with p-bromophenacyl bromide (p-BPB 10 microM) inhibited the vasodilator response to cryptolepine 2.5, 5, and 10 micrograms to 10.2 +/- 1.8, 15.9 +/- 1.5, and 20.2 +/- 2.0 mm Hg, respectively (p < 0.01). The vasodilator response to acetylcholine (ACh 50 ng) was also reduced from a control value of 56.7 +/- 4.5 to 15.3 +/- 1.9 mm Hg (p < 0.01); responses to sodium nitroprusside (SNP 5 micrograms) and isoprenaline (1 microgram) were not affected. In kidneys treated with hydroquinone (10(-5) and 10(-4) M), a specific inhibitor of endothelium-dependent vasodilation, cryptolepine- and ACh-induced vasodilation were inhibited dose dependently (p < 0.01). N omega-nitro-L-arginine (L-NNA 10(-5)-10(-4) M), a specific inhibitor of the synthesis/release of endothelium-derived relaxing factor/nitric oxide (EDRF/NO), attenuated the vasodilator response to cryptolepine and ACh (50 ng) dose dependently. At 10(-4) M L-NNA, cryptolepine-induced vasodilation was reduced to 6.6 +/- 2.2 (2.5 micrograms), 10.9 +/- 2.2 (5 micrograms), and 13.3 +/- 1.4 mm Hg (10 micrograms). L-Arginine (10(-4) and 3 x 10(-4) M) but not D-arginine (10(-4) M) inhibited the effects of L-NNA, with vasodilatory effects of cryptolepine returning to control values, suggesting that the vasodilator material released by cryptolepine is EDRF, possibly NO. Methylene blue (MB 10(-4) M), the inhibitor of soluble guanylate cyclase which inhibited 50 ng ACh and 5 micrograms SNP-induced vasodilation also reduced the vasodilatory responses to cryptolepine to 0.8 +/- 0.8 (2.5 micrograms), 4.2 +/- 4.2 (5 micrograms), and 10.8 +/- 6.2 mm Hg (10 micrograms) suggesting that the effector pathway for cryptolepine-induced vasodilation is soluble guanylate cyclase-linked increase in cyclic GMP of vascular smooth muscle.
Oyekan
A O
AO
Faculty of Medical Sciences, School of Veterinary Medicine, University of the West Indies, St. Augustine.
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D006152:Cyclic GMP / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D006873:Hydroquinones / Q000494:pharmacology; D066298:In Vitro Techniques; D026121:Indole Alkaloids; D007211:Indoles; D007668:Kidney / Q000098:blood supply*; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019335:Nitroarginine; D011189:Potassium Chloride / Q000494:pharmacology; D011804:Quinolines; D051381:Rats; D014665:Vasodilator Agents / Q000494:pharmacology*
D000470:Alkaloids; D000959:Antihypertensive Agents; D006873:Hydroquinones; D026121:Indole Alkaloids; D007211:Indoles; D011804:Quinolines; D014665:Vasodilator Agents; D019335:Nitroarginine; D009569:Nitric Oxide; C024015:cryptolepine; D011189:Potassium Chloride; D001120:Arginine; D006152:Cyclic GMP; D008751:Methylene Blue; C031927:hydroquinone