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 deficiency and mineralocorticoids on the long-term control of blood pressure and renal and endocrine variables. Six groups of uninephrectomized male Wistar rats were used: control animals and rats that received (1) N(G)-nitro-L-arginine methyl ester (L-NAME) subpressor (0.5 mg/100 mL drinking fluid), (2) L-NAME pressor (35 mg/100 mL drinking fluid), (3) deoxycorticosterone acetate (DOCA; 12. 5 mg/wk per rat), (4) DOCA plus L-NAME subpressor, or (5) L-NAME pressor plus DOCA. For all groups, the drinking fluid was tap water or 1% NaCl solution. We measured the time course of tail systolic blood pressure (SBP) and body weight for 3 weeks in all rats. At the end of the experimental period, we measured mean arterial pressure (direct recording) and endocrine and renal variables. Tail SBP rose significantly in the DOCA plus L-NAME subpressor-treated group but remained at normotensive levels in the DOCA-treated group. The addition of L-NAME to the subpressor dose accelerated the blood pressure increase in DOCA-salt hypertensive rats. The simultaneous administration of DOCA and L-NAME increased blood pressure and mortality rates in rats that drank water or saline compared with the rats treated with L-NAME alone. The subpressor dose of L-NAME did not increase blood pressure in saline-drinking rats. We conclude that impaired NO synthesis results in increased sensitivity to the pressor effect of mineralocorticoids in the presence or absence of an increased saline intake. Hence, nitric oxide contributes to the adaptative response to mineralocorticoid excess, perhaps through the facilitation of natriuresis and, thus, control of blood pressure.
Alvarez
G
G
Departamento de Fisiología, Facultad de Medicina, Servicio de Nefrología, Unidad Experimental, Granada, Spain.
Osuna
A
A
Wangensteen
R
R
Vargas
F
F
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D003900:Desoxycorticosterone / Q000494:pharmacology; D004326:Drinking; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006977:Hypertension, Renal / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008901:Mineralocorticoids / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009318:Natriuresis / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride / Q000494:pharmacology; D014667:Vasopressins / Q000378:metabolism / Q000652:urine
D004791:Enzyme Inhibitors; D008901:Mineralocorticoids; D014667:Vasopressins; D009569:Nitric Oxide; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D019331:NG-Nitroarginine Methyl Ester