Enhanced production of nitric oxide in aortae from spontaneously hypertensive rats by interleukin-1 beta.
Cultured aortic smooth muscle cells from spontaneously hypertensive rats produce more nitrite than cells from Wistar-Kyoto rats in response to interleukin-1 beta. Therefore, the effect of interleukin-1 beta-induced nitric oxide production was compared on the contractility of aortic smooth muscle from spontaneously hypertensive and Wistar-Kyoto rats. Under control conditions, there was no difference in the response of aortic rings (without endothelium) to phenylephrine between both strains. Contractions to 5-hydroxytryptamine were larger in preparations from hypertensive than normotensive animals. Treatment with interleukin-1 beta for 6 h reduced the responsiveness to both vasoconstrictors in a concentration-dependent manner. The depression was more pronounced in rings from spontaneously hypertensive rats: the threshold concentration of the cytokine was lower, and its maximal effect greater. Nitro-L-arginine prevented the inhibitory effect of interleukin-1 beta. The cytokine evoked a time-dependent loss of tone in phenylephrine-contracted rings with the same time of onset in both strains. However, the decay of tension was more pronounced in aortae from hypertensive than normotensive rats. In aortae from both strains, the decay was potentiated by L-arginine, but not D-arginine. Interleukin-1 beta elicited greater concentration-dependent productions of cyclic GMP and nitrite in rings from spontaneously hypertensive than from Wistar-Kyoto rats, and these were inhibited by methylene blue and nitro-L-arginine, respectively. The concentration-relaxation curves to 3-morpholino-sydnonimine were moderately, but significantly, shifted to the left in aortae from spontaneously hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
D C
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Junquero
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Schini
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Scott-Burden
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Vanhoutte
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D046508:Culture Techniques; D006152:Cyclic GMP / Q000096:biosynthesis; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012701:Serotonin / Q000494:pharmacology
D007375:Interleukin-1; D009573:Nitrites; D010656:Phenylephrine; D009569:Nitric Oxide; D012701:Serotonin; D006152:Cyclic GMP