Antihypertensive efficacy and effects of nitrendipine on cardiac and renal hemodynamics in mild to moderate hypertensive patients: Randomized controlled trial versus hydrochlorothiazide

Abstract

In this study antihypertensive efficacy, safety, and the effects of short-term nitrendipine administration on central and renal hemodynamics were evaluated in mild to moderate hypertensives. Our final goal was to ascertain whether the reduction in blood pressure induced by nitrendipine treatment was associated with maintained renal function. After a run-in period with placebo, 26 hypertensives without cardiac or renal disease were randomly assigned to a double-blind 8-week controlled trial with nitrendipine (N) 20 mg once a day (13 pts) or hydrochlorothiazide (HCT) 25 mg once a day (13 pts). Renal hemodynamic measurements included effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) by radionuclide study using I-131 hippuran and Tc-99m, according to the methods described by Schlegel and Gates, respectively. Effective renal blood flow [ERBF = ERPF/(1-Ht)], filtration fraction (FF = GFR/ERPF), and renal vascular resistance (RVR = MBP x 80/ERBF) were also calculated. Other hemodynamic measurements included cardiac index (CI), left ventricular (LV) ejection fraction (EF), and total peripheral resistance (TPR) measured by the first-pass radionuclide angiography technique. At the end of N or HCT administration significant decreases (p less than 0.001) in SBP, DBP, and MBP vs. baseline values were observed in both hypertensive groups. In the N group a significant decrease (p less than 0.01) in TPR and RVR, and significant increases (p less than 0.05) in CI, ERPF, and ERBF were observed. In the HCT group a significant decrease (p less than 0.05) in RVR was found without significant changes in other hemodynamic parameters. No important side effects were observed with either therapy. In conclusion, nitrendipine was effective in reducting blood pressure in mild to moderate hypertensive patients and exerted favorable effects on cardiac and renal function.

Effects of antihypertensive drugs on various aspects of renal function

“…All patients were maintained on a diet containing 150 mmol sodium per day. Using somewhat less reliable methods to measure renal plasma flow and glomerular filtration rate, they found a significant fall in renal vascular resistance without changes in flow, filtration rate, and filtration fraction at the end of the study period [3]. Despite the differences in methodology, the data all point in the same direction: Long-term treatment with a thiazide drug induces a favorable renal hemodynamic response in maintaining renal function.…”

Mathematical modeling of antihypertensive therapy

“…As other targets of HCTZ in the model, we considered constant levels of urea and potassium in the blood. Since HCTZ increases blood urea and decreases blood potassium ( Scaglione et al, 1992 ; Scaglione et al, 1995 ; Devineni et al, 2014 ), we multiplied these parameters by the factors and (the modules “Hormonal system” and “Aldosterone”, respectively).…”

“…In the model, we consider two dosages of aliskiren, 150 and 300 mg. If we denote the corresponding indicators of the drug as Aliskiren 150 and Aliskiren 300 , then the value of DRI is calculated by the formula: et al (1996) taking into account the following long-term dynamics: PRA increases by 45% (Villamil et al 2007); HR, ECFV, GFR, and CO do not significantly change (van Brummelen et al 1980, Shah et al 1978, Scaglione et al 1992, Scaglione et al 1995 (1996).…”

“…Hormonal system Urea level in the blood + 0.100 Assumed from the blood urea response to HCTZ 25 mg in Scaglione et al (1992).…”

Nitrendipine and amlodipine mimic the acute effects of enalapril on renal haemodynamics and reduce glomerular hyperfiltration in patients with chronic kidney disease

“…[12][13][14][15] Instead, there is some controversy as to the intrarenal haemodynamic effects of second generation dihydropyridinic calcium antagonists, as their vasodilatory effect on the efferent arteriole may vary according to the drug used. [16][17][18][19][20][21][22][23][24] In particular, the results of some studies suggest that amlodipine (AML) does not significantly reduce postglomerular resistances, 20,[22][23][24] whereas others have shown that amlodipine, nitrendipine (NIT) and other second-generation dihydropyridinic calcium antagonists induce haemodynamic variations suggesting a mainly efferent vasodilatory effect. [16][17][18][19]21 Unfortunately, as the method is highly complex, it has only been possible to carry out studies of the intrarenal haemodynamic effects of antihypertensive drugs on relatively small patient samples, and the assumption that calcium antagonists in general have only limited efficacy in reducing glomerular hyperfiltration has remained strong.…”