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-type calcium channels and AT1 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 both dihydropyridine and AT1 receptors was observed in SHR at 24 weeks, compared to age-matched control Wistar-Kyoto (WKY) rats (dihydropyridine receptor Bmax: 1. 30+/-0.09 vs 1.14+/-0.06 pmol mg-1 proteins, P<0.001; AT1 receptor Bmax: 1.35+/-0.07 vs 2.62+/-0.08, P<0.001 pmol mg-1 proteins). A treatment for 10 weeks with ramipril induced a significant decrease in the left ventricular mass index of SHR, as well as a significant decrease in dihydropyridine receptor density (Bmax: 0.96+/-0.01 vs 1. 39+/-0.08 pmol mg-1 proteins, P<0.001) and a significant increase in AT1 receptor density (Bmax: 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 decrease in left ventricular mass after treatment with ramipril may be dependent on changes in L-type calcium channels other than the direct effect on circulating and tissue angiotensin II (ang II) levels: involvement of calcium channels and subsequent calcium influx into cardiac cells could be proposed as an additional mechanism for the regression of left ventricular mass after ACE-inhibition.
Vulpis
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Department of Internal Medicine, DIMO, Piazza G. Cesare, 11, Bari, 70124, Italy.
Lograno
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MD
Seccia
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Pirrelli
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A
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D020746:Calcium Channels, L-Type; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D006973:Hypertension / Q000235:genetics / Q000378:metabolism*; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy*; D008297:Male; D017257:Ramipril / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000378:metabolism; D013045:Species Specificity; D013599:Systole; D016277:Ventricular Function, Left / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D017257:Ramipril