L-TYPE CALCIUM CHANNELS MODULATE THE REGRESSION OF LEFT-VENTRICULAR HYPERTROPHY AFTER ACE-INHIBITION IN GENETIC-HYPERTENSION

The aim of this study was to investigate the possible link between the regression of the left ventricular mass induced by ACE-inhibition and L-type calcium channels. For this purpose, an evaluation of both L-ty pe calcium channels and AT, receptor patterns in the left ventricular tissue of adult spontaneously hypertensive rats (SHR) was made before and after long-term treatment with ramipril. An abnormal density of bo th dihydropyridine and AT, receptors was observed in SHR at 24 weeks, compared to age-matched control Wistar-Kyoto (WKY) rats (dihydropyridi ne receptor B-max: 1.30 +/- 0.09 vs 1.14 +/- 0.06 pmol mg(-1) proteins , P < 0.001; AT(1) receptor B-max: 1.35 +/- 0.07 vs 2.62 +/- 0.08, P < 0.001 pmol mg(-1) proteins). A treatment for 10 weeks with ramipril i nduced a significant decrease in the left ventricular mass index of SH R, as well as a significant decrease in dihydropyridine receptor densi ty (B-max: 0.96 +/- 0.01 vs 1.39 +/- 0.08 pmol mg(-1) proteins, P < 0. 001) and a significant increase in AT(1) receptor density (B-max: 3.08 +/- 0.26 vs 2.78 +/- 0.09 pmol mg(-1) proteins, ramipril-treated SHR vs vehicle-treated SHR, P < 0.001). These results suggest that the dec rease in left ventricular mass after treatment with ramipril may be de pendent on changes in L-type calcium channels other than the direct ef fect on circulating and tissue angiotensin II (ang II) levels: involve ment of calcium channels and subsequent calcium influx into cardiac ce lls could be proposed as an additional mechanism for the regression of left ventricular mass after ACE-inhibition. (C) 1998 The Italian Phar macological Society.