Effect of celiprolol on large and small arteries of the forearm circulation in hypertensive patients

Abstract

Celiprolol, a new highly cardioselective beta blocker, also has direct vasodilating properties. Since the noninvasive echo Doppler technique applied to the forearm circulation (brachial artery) allows the differentiation of arteriolar vasodilation (revealed by the increasing arterial blood flow velocity) from vasodilation of large arteries (shown by an increase in arterial diameter), it seems important to study the site of celiprolol's vasodilating effect. Thirty-five hypertensive patients, (21 male, 14 female; mean age, 59 +/- 11, range 42-79 years) were treated with increasing doses of celiprolol, 200 and 400 mg, over 15 days. The duplex echo Doppler technique (Aloka 7.5 M Hz probe) was used before and during each celiprolol dose period. Statistical analysis was performed by Student's paired t test. It was observed that celiprolol significantly increases the brachial artery diameter in a dose-dependent manner, and also increases the blood flow velocity (not being direct dose-related). Since the increase in diameter was clear with a higher dose, a dose-dependent increase in blood volume, a decrease in peripheral resistance, and an increase in compliance followed. Since the higher dose of celiprolol did not further reduce blood pressure (BP) in comparison to the lower dose, and a dose-dependent increase in arterial diameter and compliance occurred and a vasodilating effect of celiprolol on arterial wall ensued that was not related to BP. In conclusion, in the doses used, celiprolol dilates both arterioles and large arteries, but the mechanism of action needs to be clarified.

Local Pulse Pressure and Regression of Arterial Wall Hypertrophy During Long-Term Antihypertensive Treatment

“…The reduction in carotid PP was likely due, at least in part, to the improvement in large artery elastic properties by celiprolol and enalapril, which have also demonstrated this effect in previous studies. 13,15 The major finding of the present study is that antihypertensive treatment reduced carotid wall thickness through the lowering of local PP rather than MBP. Interestingly, the effects of PP lowering on IMT reduction were not observed at the site of the RA.…”

“…[12][13][14] Aortic peak flow, which influences PP, was not measured in the present study. Celiprolol, because of its partial agonism, and ACEI did not change aortic peak flow in hypertensive patients, 12,19 in contrast to the ␤-blocker metoprolol.…”

“…1,11 In addition, ␤-adrenoceptor antagonists can decrease central PP by changing the characteristics of left ventricular ejection. 11 In the present study, celiprolol, a partial ␤ 1 -adrenoceptor agonist, 12 was selected for its vascular ␤ 2 -adrenoceptor agonist properties, leading to vasodilation of conducting 13 and resistive 14 arteries and improvement in arterial compliance in hypertensive humans 13 and rats. 14 We hypothesized that this pharmacological profile would favor a greater reduction in central PP than that observed with classic vasodilators, such as ACE inhibitors (ACEIs), known to improve large artery compli-ance in hypertensive patients.…”

Are we misunderstanding beta-blockers

“…Others [139] have noted that while atenolol significantly lowers mean systolic peripheral blood pressure there is a relative absence of effect upon central systolic blood pressure compared to an ACEinhibitor/diuretic combination which, by its action of slowing pulse-wave velocity and reducing the magnitude of wave reflection from periphery to aorta, markedly lowers central systolic blood pressure. Agents with beta-2/3 intrinsic sympathomimetic activity, such as nebivolol [140], pindolol [141] and celiprolol [142] improve compliance, as does labelolol [143] with additional alpha-blocking properties, and highly beta-1 selective bisoprolol [144]. The beta-blocker differences become more comprehensible when it is appreciated that beta-2 stimulation causes vasodilatation, benefits arterial elasticity and lowers central aortic pressure (augmentation index) [145,146]; beta-2 blockade would antagonise this potentially beneficial process.…”

Celiprolol

“…Roman et al 42 utilized duplex echo Doppler techniques to determine the site of celiprolol’s vasodilating effect. Thirty-five hypertensive patients were treated with increasing doses of celiprolol, 200 and 400 mg, over 15 days.…”