SYMPATHETIC FUNCTIONS IN N-G-NITRO-L-ARGININE-METHYL-ESTER-INDUCED HYPERTENSION - MODULATION BY THE RENIN-ANGIOTENSIN SYSTEM

Background Nitric oxide and angiotensin II have been shown to attenuat e cardiac beta-adrenergic inotropism. Objective To study sympathetic p resynaptic and postsynaptic functions after chronic nitric oxide synth esis blockade with N-G-nitro-L-arginine-methyl-ester (L-NAME, for 40 d ays) in association with renin-angiotensin system blockade (during the last 12 days) in order to evaluate the possible physiological interac tions between these systems. Methods Haemodynamic parameters in consci ous rats were assessed. Release of noradrenaline from isolated atria a nd cardiac beta-adrenergic-adenylyl cyclase pathway in rats of sham-tr eated and L-NAME-treated groups, with or without losartan or enalapril at treatment, were assessed. Results L-NAME-treated rats developed a t ime-dependent increase in blood pressure associated with increased pla sma adrenaline levels whereas plasma noradrenaline and cardiac catecho lamine levels were similar to those in sham-treated rats. Field-stimul ated release of noradrenaline, cardiac beta-adrenoceptor density and a ffinity and isoproterenol-stimulated formation of cyclic AMP were simi lar in sham and L-NAME-treated rats. However, Gpp(NH)p, NaF and forsko lin-stimulated adenylyl cyclase activity were greater in L-NAME rats a lthough Gs and Gi protein levels were similar in sham-treated and L-NA ME-treated rats. Losartan and enalaprilat treatments exerted equipoten t angiotensin-pressor response blockade and hypotensive effects wherea s catecholamine levels were not altered. Interestingly, only losartan treatment acted to reduce the increased Gs-adenylyl cyclase activity i n L-NAME rats, without alteration of G protein levels. Conclusions The nitric oxide synthase blockade-induced hypertension seems to be assoc iated with increased adrenal-medullary system and renin-angiotensin sy stem activities. The increased Gs-adenylyl cyclase activity after chro nic inhibition of formation of nitric oxide suggests that nitric oxide plays a modulatory role in formation of cyclic AMP, to which angioten sin II seems to contribute through an angiotensin II type 1 receptor-m ediated mechanism. (C) 1998 Rapid Science Ltd.