ENHANCED PRODUCTION OF NITRIC-OXIDE IN AORTAE FROM SPONTANEOUSLY HYPERTENSIVE RATS BY INTERLEUKIN-1-BETA

Cultured aortic smooth muscle cells from spontaneously hypertensive ra ts produce more nitrite than cells from Wistar-Kyoto rats in response to interleukin-1beta. Therefore, the effect of interleukin-1beta-induc ed 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 a ortic rings (without endothelium) to phenylephrine between both strain s. Contractions to 5-hydroxytryptamine were larger in preparations fro m 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 concentratio n of the cytokine was lower, and its maximal effect greater. Nitro-L-a rginine prevented the inhibitory effect of interleukin-1beta. The cyto kine 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 normot ensive rats. In aortae from both strains, the decay was potentiated by L-arginine, but not D-arginine. Interleukin-1beta elicited greater co ncentration-dependent productions of cyclic GMP and nitrite in rings f rom spontaneously hypertensive than from Wistar-Kyoto rats, and these were inhibited by methylene blue and nitro-L-arginine, respectively. T he concentration-relaxation curves to 3-morpholino-sydnonimine were mo derately, but significantly, shifted to the left in aortae from sponta neously hypertensive rats. These data suggest that interleukin-1beta i nduces a greater production of nitric oxide in aortic smooth muscle fr om spontaneously hypertensive than Wistar-Kyoto rats. This results in a higher and long-lasting activation of soluble guanylate cyclase, whi ch in turn impairs contractility of vascular smooth muscle to a larger extent in the hypertensive strain.