ATRIAL-NATRIURETIC-FACTOR IN 2 KIDNEY - 2 CLIP RENOVASCULAR HYPERTENSION IN THE RAT

Hig levels of circulating atrial natriuretic factor (ANF) have been re ported in several physiopathologic conditions like hypertension, heart and renal failure, pregnancy and high sodium intake. Nevertheless, ne ither relationships with water-sodium space regulation nor the role of an ANF vascular relaxant effect have been yet defined. The aim of pre sent experiments was to characterize the contribution of circulating A NF and its vascular relaxing effects in the two kidney-two clip (2K2C) experimental model of renovascular hypertension. Complementary, plasm a metabolites nitrite/nitrate of nitric oxide (NO) was examined becaus e of mediation for both (NO an ANF) through cGMP. The results showed ( two-four weeks after surgery): indirect sistolic blood pressure (mmHg) , 186 +/- 4 in HT and 122 +/- 1 in SH (p < 0.001); a significant incre ase of plasma ANF (fmol/ml) in HT (n = 7, 1221 +/- 253) vs. SH (n = 9, 476 +/- 82; p < 0.02). Nitrate/nitrite plasma concentrations (mu mol/ l) were mpt different between SH and. The relaxant effect of ANF (10(- 9), 10(-8) and 10(-7) M) on phenylephrine (3,5 x 10(-6) M) contracted rings from HT rats was smaller than SH rats (10(-8) M, p < 0.05). Cont ractions to phorbol 12, 13-dibutyrate (seven weeks after surgery) were significantly higher in rings from HT rats (p < 0.001). We conclude: 1) in addition to decreased granularity in atrial myocardiocytes, high circulating values of ANF here described suggest an increased turnove r of the peptide in 2K2C hypertensive rats; 2) lower significant vascu lar relaxant effects in HT rats would indicate down regulation of ANF receptors in this model; the latter would derive from high plasma ANF concentration and, tentatively, because of greater activity of protein kinase C in the vascular wail; 39 similar values of plasma nitrite/ni trate in SH and HT rats would indicate a comparable NO circulating ava ilability in both groups.