Chlorthalidone-modulated vascular responses to vasodilator stimuli in DOCA-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 concentrations (Cae2+) in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Half of the DOCA-salt hypertensive rats were simultaneously 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 levels of the normotensive groups. The basal perfusion pressure of the isolated mesenteric vascular bed (MVB) was not modified by Cae2+ changing or previous addition of ouabain. At normal and low Cae2+ the vasodilator effect of Ach in the MVB was reduced (P < 0.01) in DOCA-salt and less (P < 0.05) in the salt-control rats. Chlor shifted the curve of DOCA-salt backward to control group curves. In high Cae2+ the vasodilator responses to Ach were reduced (P < 0.01) both in normal-control and DOCA-salt+Chlor but not in salt-control but not in salt-control and DOCA-salt group. The vasodilator effect of ADP to different Cae2+ was similar in presence of normal and low Cae2+ in normal-control rats and it was reduced (P < 0.01) in presence of high Cae2+ in the DOCA-salt group. Chlor restored the responses to ADP to normal-control level. Under ouabain-treatment, the vasodilation duration was reduced (P < 0.05) in all groups. It was shorter (P < 0.01) in DOCA-salt than in the other ones. Chlor completely abolished this difference. The MAP reduction in DOCA-salt rats by chlor could also be associated with a restored normal responsiveness of endothelial cells to endogenous vasodilator, for example Ach and ADP, since sodium nitroprusside did not exhibit differences among the various treatments. This diuretic agent seems to elicit its effect through a reduction in plasma sodium content of DOCA-salt hypertensive rats.