Question

Which of the following antihypertensive agents is converted to nitric oxide (NO) group relaxing blood vessels?

Answer 1

Antihypertensive agents may not be equally effective in preventing hypertensive injuries due to the various forms of hypertension.Recent studies in rats and humans suggest that angiotensin converting enzyme (ACE) inhibitors significantly reduce the rate of impairment of renal function in chronic renal disease and hypertension.However, controversy exists regarding the effects of calcium channel blockers on progressive renal injury, with both positive and negative results having been reported.Although the ability of ACE inhibitors to prevent glomerular damage and left ventricular hypertrophy has been established in hypertension ,the mechanisms through which these agents prevent hypertensive injury to the glomerulus and myocardium have not been clarified. Studies performed on isolated conduit arteries in vitro, primarily the aorta, demonstrate that the release of nitric oxide (NO) in response to an endothelium-dependent vasodilator was reduced in several models of hypertension, and that an ACE inhibitor could prevent or reverse the endothelial dysfunction in hypertensive animals. In a previous study,we demonstrated a diminished production of NO and an exaggerated vasoconstrictor response to norepinephrine in the one-kidney, one-clip model of renal hypertension in rats. We also demonstrated that the increased contractile responses of the aorta to norepinephrine due to the endothelial dysfunction in these rats were normalized by administration of the ACE inhibitors captopril or enalapril, but not by the calcium channel blocker nicardipine.These results suggest that the restoration of endothelial function by an ACE inhibitor may protect the organs against hypertensive injury.ACE inhibitors reduce the formation of angiotensin II and prevent the degradation of bradykinin, an endothelium-dependent relaxant that works by stimulating the release of NO.It is thus suggested that part of the protective action of the ACE inhibitors against hypertensive injury is mediated by NO. It was recently reported that the chronic blockade of NO synthesis by the oral administration of the L-arginine analogue, NG-nitro-L-arginine methyl ester (L-NAME), caused severe systemic hypertension, glomerular damage, albuminuria, and left ventricular hypertrophy in rats. In this model of hypertension, the production of NO is selectively inhibited. Therefore, although the ACE inhibitor reportedly reversed the systemic hypertension induced by the long-term blockade of NO synthesis, it is uncertain whether the ACE inhibitors per se can prevent tissue injury in this model.Our present objective was to evaluate the involvement of NO in the protective effect of ACE inhibitors against hypertensive injury. We attempted to compare the effects of angiotensin-converting enzyme inhibition with calcium channel blockade to ascertain whether hypertension, left ventricular hypertrophy, and nephrosclerosis could be prevented during the long-term inhibition of NO synthase.

Antihypertensive drugs such as calcium channel blocker, amlodipine, alpha 1-adrenoceptor blocker, doxazosin and angiotensin converting enzyme (ACE) inhibitor, imidapril on nitric oxide synthase (NOS) activity in the kidneys of L-NAME-induced hypertensive rats. An increased blood pressure in L-NAME-induced hypertensive rats was significantly decreased by these antihypertensives to the same extent at four weeks. Nitrite production from the kidney slices was significantly suppressed in L-NAME-induced hypertensive rats. This suppression of nitrite production was reversed to the control level in the rats treated with amlodipine, and significantly enhanced by doxazosin and imidapril. Immunoreactivity for both the brain-type NOS in the macula densa and endothelial cell-type NOS in renal vasculature was diminished in L-NAME rats, and antihypertensive therapies, especially doxazosin and imidapril, increased NOS immunostaining. The increased glomerulosclerosis score in the L-NAME group was significantly lowered by the treatment with doxazosin and imidapril. In conclusion, a decreased NOS activity in L-NAME-induced hypertensive rats was significantly increased by alpha 1-adrenoceptor blockers and ACE inhibitors in the kidney, and this increased NOS activity may have a role in the prevention of glomerulosclerosis.