alpha-Vascular responses after short-term and long-term inhibition of nitric oxide synthesis

Apart from the direct actions of nitric oxide (NO) on vascular smooth muscl e, this factor may regulate cardiovascular functions through specific actio ns on alpha -adrenergic constrictor mechanisms. In this study we aim to est ablish whether the inhibition of the synthesis of this mediator could alter the vasoconstrictor responses mediated by alpha -adrenoceptor stimulation. We have been able to demonstrate that the blockage of the NO synthase real ly does exist, when both short- and long-term treatments with N-omega-nitro -L arginine methyl ester (L-NAME) are carried out. We have evaluated the co ncentration-dependent contractions induced by the selective alpha (1)-adren oceptor agonists methoxamine and phenylephrine in isolated rat aorta rings in the following groups of animals: control, short-term L-NAME-treated (100 mg/kg i.p, 20 min before subjecting the animals to the experiments) and lo ng-term L-NAME-treated (100 mg/kg per day in the drinking water for 7, 21, or 45 days). We have also evaluated the presser responses to methoxamine an d to the selective alpha (2)-adrenoceptor agonist B-HT 920 using the pithed rat preparation in the same groups of animals. The contractile responses t o methoxamine and phenylephrine were similar in the rat aorta preparations from control and short-term L-NAME-treated animals. On the contrary, in the rat al,rta preparations from long-term L-NAME-treated animals these respon ses were clearly reduced when compared with the corresponding responses in those from control animals, the reduction being more marked when the treatm ent lasted longer. The presser responses to methoxamine were also similar i rt control and short-term L-NAME-treated pithed rats. Nevertheless, the res ponses to B-HT 920 were greater in the latter. On the other hand, the dose- response curves to both alpha -adrenoceptor agonists were shifted to the ri ght in a non-parallel manner in rats treated long term with L-NAME, the shi ft being, in the case of B-HT 920, more accentuated when the treatment last ed 21 or 45 days than when it lasted only 7 days. These results indicate th at the short-term decrease in NO synthesis does not modify the vascular smo oth muscle responses mediated by alpha (1)-adrenoceptor stimulation, but it does induce a potentiation of sympathetic vasoconstriction mediated by alp ha (2)-adrenoceptors. Nevertheless, the long-term inhibition of NO synthesi s causes a compensating decrease in the alpha (1)- and alpha (2)-vascular s mooth muscle contractile responses.