Effect of antihypertensive treatment and N?? -nitro-L-arginine methyl ester on cardiovascular structure in deoxycorticosterone acetate-salt hypertensive rats
Deoxycorticosterone acetate (DOCA)-salt hypertensive rats exhibit a very severe degree of cardiovascular hypertrophy, which may in part be mediated by overexpression of the endothelin-1 gene. To examine the effects of the angiotensin I converting enzyme inhibitor cilazapril and of the calcium channel antagonist mibefradil, both of which may affect potential mechanisms responsible for hypertrophy of cardiovascular structures, and that of the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), which may exert a paradoxical inhibitory effect on cardiovascular growth, on the severe cardiovascular hypertrophy of DOCA-salt hypertensive rats and on arterial expression of the endothelin-1 gene. Small-artery structure was examined on a wire myograph and endothelin-1 messenger RNA (mRNA) was quantified by Northern blot analysis. Cilazapril did not affect blood pressure, cardiovascular structure or the increased abundance of endothelin mRNA of DOCA-salt hypertensive rats. Mibefradil treatment resulted in lower blood pressure, reduced cardiac hypertrophy, near-normal structure of conduit and small arteries and lower endothelin-1 mRNA abundance. L-NAME treatment resulted in higher blood pressure and increased severity of conduit artery hypertrophy, but reduced cardiac and small artery hypertrophy, and enhanced aortic endothelin-1 mRNA. These results suggest that the renin-angiotensin system does not play a role in cardiovascular hypertrophy in DOCA-salt hypertensive rats, which is not unexpected since plasma renin is suppressed in these rats. Calcium channel blockade may interfere with mechanisms underlying vascular hypertrophy in this model via blockade of calcium entry or by reducing vascular endothelin-1 gene expression when the blood pressure is lowered. L-NAME has been shown to exert a growth-inhibitory effect on small arteries and on the heart despite increasing blood pressure, probably independently from its ability to inhibit nitric oxide synthase, the latter of which is presumably involved in the blood pressure rise induced.