Keiko Otsuka

Haemodynamic Effects of New α-Blockers with Vasodilatory Properties in Essential Hypertension

SummarySix 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 < 0.05), dilevalol (p < 0.05), urapidil, doxazosin (p < 0.05) and altiopril groups; cardiac index was unchanged in these groups.As carvedilol and N-696 have no β1-selectivity and no intrinsic sympathomimetic activity (ISA), their direct vasodilating property (and the possible α-blocking activity of carvedilol) may precipitate in minimising an increase in TPRI induced by vascular β2blockade and suppressed cardiac pump function. Celiprolol and dilevalol, with β2-selective ISA, reduced cardiac index slightly and insignificantly, and decreased TPRI. These results indicate that ISA on vascular β2-receptors may induce vasodilatation and ISA on cardiac β2-receptors may counteract cardiac β2-blockade. Differences in haemodynamic responses between these drugs with ISA and vasodilators such as α-blocking agents (urapidil and doxazosin) and an ACE inhibitor, altiopril, may be attributable to manifestation of cardiac β-blockade as observed in the drugs with ISA.

Effect of pindolol and nifedipine alone and in combination on haemodynamic parameters/variables in essential hypertension.

Thirteen patients with essential hypertension were started on pindolol 10–20 mg daily and twelve on nifedipine 20–60 mg daily. At the end of 6 weeks inadequate responders (B.P. > 140/90) were put onto combined treatment with both drugs, ten of the pindolol and six of the nifedipine patients being affected. Combined therapy then continued for a further 6-week period, while adequate responders (B.P. < 140/90) continued with their initial drug. In addition to blood pressure, heart rate and cardiac index were also measured, and total peripheral resistance index was calculated. Where blood pressure decreased below 140/90 at the end of 12 weeks in patients on combined treatment, the original drug was withdrawn, leaving the patient on a single-drug regimen again, this time with the ‘second compound’. This manoeuvre was followed by a rise in blood pressure in five out of eight patients in whom pindolol was withdrawn and in two out of six after nifedipine withdrawal. No definite conclusions can be drawn from these findings, and it may be that a better approach to the problem of poor responders would be to try each drug on its own before combining them, rather than combining first and then withdrawing the initial treatment. The increased peripheral resistance typical of essential hypertension was not adversely affected by either drug, while combined treatment had a beneficial effect on this parameter.