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Haemodynamic effects of new beta-blockers with vasodilatory properties in essential hypertension
H Tsukiyama1, K Otsuka, M Horii
1Department of Cardiovascular Diseases, Kanagawa Cancer Center, Yokohama, Japan.
Insights
Different blood pressure medications affect heart rate and blood flow differently. Some drugs with intrinsic sympathomimetic activity (ISA) show vasodilating properties, influencing total peripheral resistance index (TPRI) and cardiac index.
Area of Science:
- Cardiovascular pharmacology
- Hemodynamics
- Drug efficacy
Background:
- Antihypertensive medications vary in their mechanisms of action.
- Understanding the hemodynamic effects of different drug classes is crucial for treatment selection.
- Beta-blockers, vasodilators, and ACE inhibitors have distinct impacts on cardiovascular function.
Purpose of the Study:
- To compare the hemodynamic effects of various antihypertensive drugs, including beta-blockers with and without intrinsic sympathomimetic activity (ISA), alpha-blockers, and an ACE inhibitor.
- To elucidate the role of ISA and direct vasodilation in the cardiovascular response to these agents.
- To differentiate the mechanisms underlying blood pressure reduction and associated changes in cardiac index and total peripheral resistance index (TPRI).
Main Methods:
- A six-week treatment study involving carvedilol, N-696, celiprolol, dilevalol, acebutolol, urapidil, doxazosin, and altiopril.
- Measurement of blood pressure, heart rate, cardiac index, and total peripheral resistance index (TPRI) before and after treatment.
- Analysis of drug properties including beta-selectivity and intrinsic sympathomimetic activity (ISA).
Main Results:
- All tested drugs reduced blood pressure, with varying effects on heart rate.
- Carvedilol, N-696, and acebutolol showed decreased cardiac index with stable TPRI.
- Celiprolol, dilevalol, urapidil, doxazosin, and altiopril demonstrated decreased TPRI and unchanged cardiac index, with some showing significant decreases (p < 0.05).
Conclusions:
- Drugs with direct vasodilating properties and alpha-blocking activity (carvedilol, N-696) may minimize TPRI increase by counteracting beta-2 blockade effects.
- Beta-2 selective ISA in celiprolol and dilevalol induced vasodilation and counteracted cardiac beta-2 blockade, leading to reduced TPRI.
- Hemodynamic differences suggest that ISA and direct vasodilation play key roles, distinguishing these agents from pure vasodilators and ACE inhibitors.
Abstract:
Six weeks of treatment with carvedilol, N-696, celiprolol, dilevalol, acebutolol, urapidil, doxazosin and altiopril reduced blood pressure with various changes in heart rate. Cardiac index decreased and total peripheral resistance index (TPRI) stayed at the pretreatment levels in the carvedilol, N-696 and acebutolol groups, whereas TPRI tended to decrease in the celiprolol (p less than 0.05), dilevalol (p less than 0.05), urapidil, doxazosin (p less than 0.05) and altiopril groups; cardiac index was unchanged in these groups. As carvedilol and N-696 have no beta 1-selectivity and no intrinsic sympathomimetic activity (ISA), their direct vasodilating property (and the possible alpha-blocking activity of carvedilol) may precipitate in minimising an increase in TPRI induced by vascular beta 2-blockade and suppressed cardiac pump function. Celiprolol and dilevalol, with beta 2-selective ISA, reduced cardiac index slightly and insignificantly, and decreased TPRI. These results indicate that ISA on vascular beta 2-receptors may induce vasodilatation and ISA on cardiac beta 2-receptors may counteract cardiac beta 2-blockade. Differences in haemodynamic responses between these drugs with ISA and vasodilators such as alpha-blocking agents (urapidil and doxazosin) and an ACE inhibitor, altiopril, may be attributable to manifestation of cardiac beta-blockade as observed in the drugs with ISA.