CHLORTHALIDONE-MODULATED VASCULAR-RESPONSES TO VASODILATOR STIMULI INDOCA-SALT HYPERTENSIVE RATS

This study was carried out to test the effect of chlorthalidone (Chlor ) treatment on the vascular responsiveness to acetylcholine (Ach) and adenosine disphosphate (ADP) under different extracellular calcium con centrations (Ca-e(2+)) in deoxycorticosterone acetate (DOCA)-salt hype rtensive rats. Half of the DOCA-salt hypertensive rats were simultaneo usly given Chlor (8 mg day(-1), p.o.), after the twentieth day of DOCA , until the fortieth day. Mean arterial pressure (MAP) was reduced (P< 0.01) in DOCA-salt-Chlor (121+/-3 mmHg) compared to DOCA-salt (175+/-3 mmHg) rats. Chlor reduced the high plasma sodium of DOCA-salt to leve ls of the normotensive groups. The basal perfusion pressure of the iso lated mesenteric vascular bed (MVB) was not modified by Ca-e(2+) chang ing or previous addition of ouabain. At normal and low Ca-e(2+) the va sodilator effect of Ach in the MVB was reduced (P<0.01) in DOCA-salt a nd less (P<0.05) in the salt-control rats, Chlor shifted the curve of DOCA-salt backward to control group curves. In high Ca-e(2+) the vasod ilator responses to Ach were reduced (P<0.01) both in normal-control a nd DOCA-salt+Chlor but not in salt-control and DOCA-salt group. The va sodilator effect of ADP to different Ca-e(2+) was similar in presence of normal and low Ca-e(2+) in normal-control rats and it was reduced ( P<0.01) in presence of high Ca-e(2+) in the DOCA-salt group. Chlor res tored the responses to ADP to normal-control level. Under ouabain-trea tment, the vasodilatation duration was reduced (P<0.05) in all groups. It was shorter (P<0.01) in DOCA-salt than in the other ones. Chlor co mpletely abolished this difference. The MAP reduction in DOCA-salt rat s by chlor could also be associated with a restored normal responsiven ess of endothelial cells to endogenous vasodilator, for example Ach an d ADP, since sodium nitroprusside did not exhibit differences among th e various treatments. This diuretic agent seems to elicit its effect t hrough a reduction in plasma sodium content of DOCA-salt hypertensive rats. (C) 1996 The Italian Pharmacological Society