Abstract

COLINA-ARAUJO, José A et al. Nephroprotection from calcium channels blocking agents: A contribution to their probable mechanism of action. Invest. clín [online]. 2008, vol.49, n.3, pp.369-385. ISSN 0535-5133.

The prevalence and incidence of end-stage renal disease have progressively increased in the last 20 years and, both Hypertension (HT) and Diabetes Mellitus (DM) are the two most important causes of such a condition. Haemodynamic and metabolic perturbations contribute to the development and progression of renal disease and both HT and DM are key factors in the nephropathy. Blood pressure reduction alone is insufficient for maximal renal protection, hence the need for the knowledge of additional mechanisms for nephroprotection in order to establish preventive measures. To contribute to the knowledge of the nephroprotective mechanism of the calcium channel blocking agents (CB) of the dihydropiridine group, this prospective, experimental, longitudinal, and placebo-controlled clinical trial was performed in 55 non-diabetic normotensive and hypertensive adults receiving 3 CB drugs at antihypertensive doses and as monodoses. There were 3 groups. A: Normotensive (n = 25) receiving a single dose of Nitrendipine 20 mg; B: Type I and II hypertensive (n = 15) receiving Nifedipine for 12 weeks; and C: Type I and II hypertensive (n = 15) receiving Amlodipine 5 mg/day, for one week. Together with clinical and hemodynamic responses, biochemical parameters such as renal vasoactive hormones renin, prostaglandins and kallikreins, nitric oxide and cGMP were measured. The antihypertensive effect of CB drugs was confirmed and there was a significant increase in urinary kallikreins excretion related to an increase in nitric oxide. It is concluded that the nephroprotective effect of CB may be due to their capacity to increase urinary kallikreins which in turn, releases nitric oxide production. It is recommended to continue this research with larger number of hypertensive and diabetic patients with nephropathy and longer clinical trials.

Keywords : Nephroprotection; calcium channels blocking agents; hypertension; renal hormones; kallikreins; nitric oxide.

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