ROLE OF NITRIC-OXIDE AND PROSTAGLANDINS IN THE REGULATION OF BLOOD-PRESSURE IN CONSCIOUS RATS

The present study was designed to investigate the possible role of endothelium-derived vasodilators, nitric oxide and prostaglandins, in the regulation of blood pressure during the presence and absence of the major presser systems. Conscious rats were infused with a cocktail of inhibitors of the sympathetic nervous system, renin-angiotensin system, and V-1 vascular receptor to vasopressin (achieved with hexamethonium, captopril, phentolamine, propranolol, and the V-1 vasopressin (AVP) antagonist des-(CH2)(5)Tyr(Me)-AVP). The cocktail of vasoconstrictor inhibitors induced a marked fall of mean arterial pressure (MAP) from 109 +/- 2 to 52 +/- 2 mmHg (1 mmHg = 133.3 Pa) (n = 24). In animals with blockade, the specific inhibitor of nitric oxide synthesis, N-G-nitro-L-arginine methyl ester (L-NAME), induced a significant increase of MAP from 51 +/- 1 to 84 +/- 2 mmHg (n = 6). In the presence of indomethacin, a cyclooxygenase inhibitor, the presser response to L-NAME was from 52 +/- 2 to 126 +/- 4 mmHg (n = 6). Neither indomethacin (n = 6) nor vehicle (n = 6) alone altered MAP. In intact animals without blockade, L-NAME caused a similar increase of MAP when it was injected alone (from 107 +/- 3 to 144 +/- 4 mmHg, n = 7) or with indomethacin (from 113 +/- 3 to 144 +/- 3, n = 6). Indomethacin alone (n = 8) did not change MAP. In conclusion, in the absence of the major presser systems, the presser effect of the inhibition of the production of endogenous nitric oxide and vasodilator prostanoid synthesis appears to be synergistic. These results suggest that these two endogenous vasodilators are involved in the maintenance of blood pressure.