HYPEROSMOLARITY ENHANCES SMOOTH-MUSCLE CONTRACTILE RESPONSES TO PHENYLEPHRINE AND PARTIALLY IMPAIRS NITRIC-OXIDE PRODUCTION IN THE RAT TAILARTERY

The respective effects of hyperosmolarity caused by impermeant solutes , such as mannitol and sucrose, on the endothelium and smooth muscles cell responses were investigated in the rat tail artery. The vessels, with or without endothelium, were infused and superfused with an isosm olar saline solution, and were repeatedly stimulated with phenylephrin e. Superfusing with hyperosmolar fluid (390-420 mosm/l) produced a tra nsient increase in the arterial basal perfusion pressure which peaked after approximately 5 min and then declined within 15 min to a stable nonsignificant value above control values in subsequent experiments. I n arteries with functional endothelium, the effect of phenylephrine wa s about 1.9-fold larger in hyperosmotic medium compared to that in iso smotic medium. In hyperosmotic media the response was still more than twofold enhanced in endothelium-denuded vessels compared to those with endothelium. In the latter, indomethacin (10 mu M) had no effect, but N-omega-nitro-L-arginine methylester (L-NAME; 30 mu mol/l), an inhibi tor of NO production, enhanced the response to phenylephrine to reach the same magnitude of response as seen in endothelium-denuded arteries . This effect of L-NAME was antagonized by L-arginine. Relaxation indu ced by the NO donor SIN-1 was unchanged by hyperosmolarity, indicating that the effect of NO was not impaired. It is concluded that, in the rat tail artery, the enhancement in phenylephrine-induced contractions produced in a hyperosmolar solution is due to both an endothelium-ind ependent increase in smooth muscle responses and a moderate decrease i n the production of NO, or an NO-like factor, by the endothelium. In s pite of this reduction, endothelium-derived NO still plays a major rol e in attenuating phenylephrine-induced contractions in hyperosmolar me dium.