OBJECTIVES: We sought to study the effects of short-acting and long-acting nifedipine on the sympathetic nervous system (SNS), heart rate (HR) and blood pressure (BP) of normotensive subjects under baseline conditions and during SNS stimulation. BACKGROUND:Calcium channel antagonists in different pharmacokinetic formulations are widely used in patients with coronary artery disease or hypertension. Short-acting formulations activate the SNS, an action that may be disadvantageous in patients with coronary disease, especially if left ventricular function is impaired. The effects of slow-release formulations on the SNS are unknown. METHODS: We used microneurography to investigate the influence of nifedipine (5 mg; 10 mg; and slow-release [GITS], 60 mg) on muscle sympathetic nerve activity (MSA) and skin sympathetic nerve activity (SSA) in healthy volunteers. RESULTS:Peak plasma levels after short-acting and slow-release nifedipine were achieved within 60 min and 330 min, respectively. Short-acting (10 mg, n = 10) and slow-release (n = 10) nifedipine, but not placebo, markedly activated MSA and increased plasma norepinephrine; plasma endothelin increased only with slow-release nifedipine. HR increased after short-acting nifedipine, but not after nifedipine GITS. Nifedipine had no effect on SSA (n = 6). Blockade of cardiac sympathetic activity (with esmolol) led to similar decreases in HR with or without nifedipine, whereas parasympatholysis (with atropine) led to similar increases in HR with or without nifedipine. The cold pressor test markedly increased MSA in all treatment groups and further increased MSA beyond the increase induced by nifedipine. CONCLUSIONS:Nifedipine markedly increased MSA, but not SSA, independently of drug release formulation. In contrast, HR increased with short-acting, but not with slow-release, nifedipine. Therefore, nifedipine activates cardiac and peripheral sympathetic nerves differently depending on pharmacokinetics. These effects of nifedipine may be disadvantageous in cardiac patients with increased sympathetic activity or congestive heart failure, or both.
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OBJECTIVES: We sought to study the effects of short-acting and long-acting nifedipine on the sympathetic nervous system (SNS), heart rate (HR) and blood pressure (BP) of normotensive subjects under baseline conditions and during SNS stimulation. BACKGROUND: Calcium channel antagonists in different pharmacokinetic formulations are widely used in patients with coronary artery disease or hypertension. Short-acting formulations activate the SNS, an action that may be disadvantageous in patients with coronary disease, especially if left ventricular function is impaired. The effects of slow-release formulations on the SNS are unknown. METHODS: We used microneurography to investigate the influence of nifedipine (5 mg; 10 mg; and slow-release [GITS], 60 mg) on muscle sympathetic nerve activity (MSA) and skin sympathetic nerve activity (SSA) in healthy volunteers. RESULTS: Peak plasma levels after short-acting and slow-release nifedipine were achieved within 60 min and 330 min, respectively. Short-acting (10 mg, n = 10) and slow-release (n = 10) nifedipine, but not placebo, markedly activated MSA and increased plasma norepinephrine; plasma endothelin increased only with slow-release nifedipine. HR increased after short-acting nifedipine, but not after nifedipine GITS. Nifedipine had no effect on SSA (n = 6). Blockade of cardiac sympathetic activity (with esmolol) led to similar decreases in HR with or without nifedipine, whereas parasympatholysis (with atropine) led to similar increases in HR with or without nifedipine. The cold pressor test markedly increased MSA in all treatment groups and further increased MSA beyond the increase induced by nifedipine. CONCLUSIONS:Nifedipine markedly increased MSA, but not SSA, independently of drug release formulation. In contrast, HR increased with short-acting, but not with slow-release, nifedipine. Therefore, nifedipine activates cardiac and peripheral sympathetic nerves differently depending on pharmacokinetics. These effects of nifedipine may be disadvantageous in cardiac patients with increased sympathetic activity or congestive heart failure, or both.
Authors: René R Wenzel; Anna Mitchell; Winfried Siffert; Sandra Bührmann; Thomas Philipp; Rafael F Schäfers Journal: Br J Clin Pharmacol Date: 2004-05 Impact factor: 4.335
Authors: C Meyer; P Schueller; J Balzer; T Lauer; R Westenfeld; P Schauerte; M Hennersdorf; S Steiner; M Kelm; T Rassaf Journal: Eur J Med Res Date: 2009-12-07 Impact factor: 2.175