COMPARATIVE EFFECTS OF INDAPAMIDE AND HYDROCHLOROTHIAZIDE ON CARDIAC-HYPERTROPHY AND VASCULAR SMOOTH-MUSCLE PHENOTYPE IN THE STROKE-PRONE, SPONTANEOUSLY HYPERTENSIVE RAT

The effects of two diuretics, indapamide (3 mg/kg/day) and hydrochloro thiazide (20 mg/kg/day), were analyzed over a 44-day period on the car diovascular hypertrophy of stroke-prone spontaneously hypertensive rat s (SHR-SP). Untreated SHR-SP developed severe hypertension and cardiac hypertrophy when compared to normotensive Wistar-Kyoto (WKY) rats aft er 8 weeks on 1% sodium chloride. In diuretic-treated animals, systoli c blood pressure was moderately decreased by the end of the treatment when compared with untreated SHR-SP (-13 and -18%, respectively, p les s-than-or-equal-to 0.05). Morphometric analysis of myocyte cross-secti onal areas evidenced that indapamide was the most effective in prevent ing myocyte hypertrophy (- 33%, p less-than-or-equal-to 0.0001). Small coronary artery wall thickness was efficiently prevented in the two t reated groups, but medial hypertrophy was prevented by hydrochlorothia zide only. Among markers of smooth-muscle cell phenotype (contractile or extracellular matrix proteins) EIIIA-fibronectin (FN), one FN cellu lar isoform, was shown to be the most sensitive marker by an immunohis tochemical technic. Medial expression of EIIIA-FN, which was character istic of SHR-SP coronary arteries, was prevented by the two treatments . The two diuretic treatments, despite similar effects on blood pressu re and smooth-muscle phenotype, prevent SHR-SP cardiovascular hypertro phy with a drug-specific efficiency.