Short-Versus Long-Term Effects of Different Dihydropyridines on Sympathetic and Baroreflex Function in Hypertension

Abstract

Abstract-Antihypertensive treatment with dihydropyridines may be accompanied by sympathetic activation. Data on whether this is common to all compounds and similar in the various phases of treatment are not univocal, however. In 28 untreated essential hypertensives (age, 56.4Ϯ1.8 years; meanϮSEM) finger blood pressure (BP, Finapres), heart rate (HR, ECG), plasma norepinephrine (NE, high-performance liquid chromatography), and muscle sympathetic nerve traffic (MSNA, microneurography) were measured at rest and during baroreceptor manipulation (vasoactive drugs) in the placebo run-in period and after randomization to double-blind acute and chronic (8 weeks) felodipine (10 mg/d, nϭ14) or lercanidipine (10 mg/d, nϭ14). Acute administration of both drugs induced pronounced BP reductions and marked increases in HR, NE, and MSNA. After 8 weeks of treatment, BP reductions were similar to those observed after acute administration, whereas HR, NE, and MSNA responses were markedly attenuated (Ϫ7%, Ϫ32%, and Ϫ14%, respectively; PϽ0.05). There was a small residual increase in sympathetic activity in the felodipine group, whereas in the lercanidipine group, all adrenergic markers returned to baseline values. Baroreflex control of HR and MSNA was markedly impaired (Ϫ42% and Ϫ48%, respectively) after acute drug administration, with a recovery and complete resetting during chronic treatment. Thus, the sympathoexcitation induced by 2 different dihydropyridines is largely limited to the acute administration. The 2 drugs have, nevertheless, a different chronic sympathetic effect, indicating that dihydropyridines do not homogeneously affect this function. The acute sympathoexcitation, but not the small between-drugs differential chronic adrenergic effect, is accounted for by baroreflex impairment. Key Words: autonomic nervous system Ⅲ sympathetic nervous system Ⅲ baroreflex Ⅲ calcium Ⅲ hypertension, essential S everal studies have shown that the hyperadrenergic state characterizing essential hypertension (1) favors the development and progression of the hypertensive state, 1-7 (2) promotes and accelerates the occurrence of the hypertensionrelated cardiac and vascular damage, 5-9 and (3) adversely modulates metabolic cardiovascular risk factors, including insulin resistance. [3][4][5]7,10 This implies that antihypertensive treatment should be based on drugs that are capable of not only effectively reducing the elevated blood pressure (BP) but also avoiding the neuroadrenergic activation that may be reflexly triggered by the BP-lowering response. 6 -8,10 -12 The effect of calcium antagonists of the dihydropyridine class on sympathetic cardiovascular drive has been investigated in a number of studies that have produced, however, different results (ie, an increase, no change, or even a decrease in sympathetic activity). [13][14][15][16][17][18][19][20] This could be due to the different pharmacokinetic and/or pharmacodynamic properties of the drugs examined. 21 It could also be accounted for, however, by the different characteristics o...

Calcium Antagonists in Arterial Hypertension Treatment: Specifics of Lercanidipine

“…Через 8 недель постоянного лечения у больных, полу-чавших фелодипин, сохранялись признаки симпати-ческой активации и нарушения барорецепторной регуляции сердечного ритма. У больных, получавших лерканидипин, ЧСС, уровень норадреналина, состо-яние барорецепторной регуляции вернулись к исход-ному уровню [5]. Именно отсутствие выраженной симпатической активации создает условия для суще-ственно лучшей переносимости лерканидипина, по сравнению с другими АК.…”

The sympathetic nervous system and blood pressure in humans: implications for hypertension

“…72 Whether these previously unrecognised pleiotropic effects of b-adrenergic blockade are manifested in human hypertension remains to be determined. Of note, despite lowering blood pressure certain diuretics (for example, chlorthalidone 73 ), dihydropridine calcium channel blockers 74 and combination therapies (for example, AT1-R antagonism plus diuretic 75 ) may actually raise SNA due to baroreceptor unloading. Said differently, assuming the baroreceptors are not desensitised by these drugs, a fall in arterial pressure may trigger a baroreflexly mediated increase in sympathetic activity and arterial pressure.…”

The effect of gender on the sympathetic nerve hyperactivity of essential hypertension

“…51 Indeed, our findings and the previously reported association between the sympathetic activation of hypertension and its cardiovascular complications 5,7,8 make it possible to argue that the choice of anti-hypertensive agents could be influenced by gender when sympathetic activation is of relevance. Some of these agents have been reported to have no effect on sympathetic activity [52][53][54][55][56] or increase it, 52,54 whereas others either curtail sympathetic activation 57 or block sympathetic effects. [54][55][56] In conclusion, hypertension in women was associated with a lower level of central sympathetic hyperactivity than in men.…”