SYSTEMIC INHIBITION OF NITRIC-OXIDE AND PROSTAGLANDINS IN VOLUME-INDUCED NATRIURESIS AND HYPERTENSION

Nitric oxide (NO) synthesis inhibition with N-G-nitro-L-arginine methy l ester (L-NAME) (10 mu g.kg(-1).min(-1) iv), cyclooxygenase inhibitio n with meclofenamate (Meclo; 5 mg/kg iv bolus), and combination of dru gs (L-NAME+Meclo) were used to investigate the roles of NO and prostag landins (PG) in the hemodynamic and natriuretic responses to isotonic saline volume expansion (VE; 5% body wt over 60 min) in anesthetized d ogs. Before VE, L-NAME (n = 6), Meclo (n = 6), and L-NAME+Meclo (n = 6 ) produced significant increments in mean arterial pressure (MAP) of 1 2 +/- 2, 15 +/- 3, and 17 +/- 3 mmHg, respectively. VE did not change MAP in Meclo-treated dogs, but produced a significant elevation in the control dogs (14 +/- 6 mmHg), in L-NAME-treated dogs (17 +/- 6 mmHg), and in dogs pretreated with L-NAME+Meclo (12 +/- 5 mmHg). VE alone in duced marked natriuretic responses in the control (38 +/- 9 to 562 +/- 86 mu mol/min), L-NAME (31 +/- 9 to 664 +/- 65 mu mol/min), and Meclo groups (41 +/- 10 to 699 +/- 51 mu mol/min). However, this natriureti c response was attenuated in dogs pretreated with L-NAME+Meclo (12 +/- 4 to 185 +/- 52 mu mol/min). These results indicate that 1) blockade of both NO and PGs has significant diminishing effects on volume-induc ed natriuresis, 2) NO blockade alone impairs volume-induced natriuresi s in a manner that requires further increases in MAP to restore the na triuresis, and 3) PC7 blockade alone does not curtail volume-induced n atriuresis.