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 end othelium-derived vasodilators, nitric oxide and prostaglandins, in the regulation of blood pressure during the presence and absence of the m ajor presser systems. Conscious rats were infused with a cocktail of i nhibitors 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 i nhibitors induced a marked fall of mean arterial pressure (MAP) from 1 09 +/- 2 to 52 +/- 2 mmHg (1 mmHg = 133.3 Pa) (n = 24). In animals wit h blockade, the specific inhibitor of nitric oxide synthesis, N-G-nitr o-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 indomet hacin, 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 block ade, L-NAME caused a similar increase of MAP when it was injected alon e (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 ch ange MAP. In conclusion, in the absence of the major presser systems, the presser effect of the inhibition of the production of endogenous n itric oxide and vasodilator prostanoid synthesis appears to be synergi stic. These results suggest that these two endogenous vasodilators are involved in the maintenance of blood pressure.