Interaction between nitric oxide and mineralocorticoids in the long-term control of blood pressure

We analyzed the effects of a possible interaction between nitric oxide defi ciency and mineralocorticoids on the long-term control of blood pressure an d renal and endocrine variables. Six groups of uninephrectomized male Wista r rats were used: control animals and rats that received (1) N-G-nitro-L-ar ginine methyl ester (L-NAME) subpressor (0.5 mg/100 mL drinking fluid), (2) L-NAME presser (35 mg/100 mL drinking fluid), (3) deoxycorticosterone acet ate (DOCA; 12.5 mg/wk per rat), (4) DOCA plus L-NAME subpressor, or (5) L-N AME presser plus DOCA. For all groups, the drinking fluid was tap water or 1% NaCl solution. We measured the time course of tail systolic blood pressu re (SBP) and body weight for 3 weeks in all rats. At the end of the experim ental period, we measured mean arterial,pressure (direct recording) and end ocrine and renal variables. Tail SEP rose significantly in the DOCA plus L- NAME subpressor-treated group but remained at normotensive levels in the DO CA-treated group. The addition of L-NAME to the subpressor dose accelerated the blood pressure increase in DOCA-salt hypertensive rats. The simultaneo us administration of DOCA and L-NAME increased blood pressure and mortality rates in rats that drank water or saline compared with the rats treated wi th L-NAME alone. The subpressor dose of L-NAME did not increase blood press ure in saline-drinking rats. We conclude that impaired NO synthesis results in increased sensitivity to the presser effect of mineralocorticoids in th e presence or absence of an increased saline intake. Hence, nitric oxide co ntributes to the adaptative response to mineralocorticoid excess, perhaps t hrough the facilitation of natriuresis and, thus, control of blood pressure .