EFFECTS OF ATRIAL-NATRIURETIC-PEPTIDE AND NITROPRUSSIDE ON ISOLATED PULMONARY RESISTANCE AND CONDUIT ARTERIES FROM RATS WITH PULMONARY-HYPERTENSION

1 The relaxant effects of atrial natriuretic peptide (ANP) and nitropr usside were studied on prostaglandin F2alpha (PGF2alpha)-Contracted pr eparations of pulmonary resistance vessels (internal diameter 200-500 mum) and main pulmonary arteries taken from rats with pulmonary hypert ension induced by monocrotaline (105 mg kg-1, s.c., 4 weeks previously ). Control rats received saline. 2 In preparations from monocrotaline- treated rats, the potencies (negative log EC50) of ANP on resistance v essels (8.45) and main pulmonary arteries (8.25) were similar to those obtained in vessels from control rats (8.78 and 8.53 respectively), w hereas those of nitroprusside were significantly less than in controls in both resistance vessels (7.13 compared with 7.63 in controls; thre e fold decrease in potency) and main pulmonary arteries (6.92 compared with 8.17 in controls; 18 fold decrease in potency). 3 On pulmonary r esistance vessels from monocrotaline-treated rats, the maximum relaxan t responses to ANP and nitroprusside, and also to pinacidil, were incr eased compared with controls, and reversal of the PGF2alpha-induced co ntraction by these drugs was greater than 100%. In contrast, on main p ulmonary arteries from monocrotaline-treated rats, the maximum relaxat ions to ANP and nitroprusside were not increased relative to controls, and reversal of PGF2alpha was not greater than 100%. 4 Since the high potency of ANP on pulmonary resistance and conduit arteries is retain ed in vessels from rats with pulmonary hypertension, whether induced b y monocrotaline (this study) or by chronic hypoxia (previous findings) , it is postulated that elevation of plasma levels of ANP by use of dr ugs that inhibit the breakdown of this endogenous peptide, may be one approach to the pharmacological treatment of pulmonary hypertension.