Alpha- and beta-adrenergic receptor blockade in the treatment of hypertension.

Abstract

The effects of single and combined selective blockade of the sympathetic alpha-and beta-receptors were examined in patients with severe hypertension (diastolic pressure > I20 mmHg) uncomplicated by cardiac or renal failure. Given In uncomplicated essential hypertension the raised blood pressure is accompanied by a normal cardiac output (Taylor, Donald, and Bishop, I957). The increased peripheral resistance is uniformly distributed throughout all the regional circulations and resides predominantly in the peripheral arterioles (Freis, I960). These vessels regulate the resistance in many of the regional vascular beds, and particularly in the kidney, through sympathetic alphaadrenergic receptors (Moran, I966).Thus it is reasonable to expect that drugs which possess both vasodilator properties and also the ability to inhibit stimulation of the adrenergic alpha-receptors may offer substantial advantages over other less specific agents in the treatment of hypertensive vascular disease. Phentolanine, an alpha-receptor antagonist with conspicuous vasodilator properties (Taylor et al., i965a, b; Majid, Sharma, and Taylor, 197i), has been shown to be effective in acutely lowering the blood pressure of hypertensive patients (Taylor et al., i965a I965a; Majid et al., 197I). For this reason it is logical to combine drugs that block both the alphaand beta-adrenoreceptors so that the reflex increase in sympathetic stimulation of the heart that occurs in response to the fall in blood pressure induced by alpha-receptor blockade is prevented by inhibition of the cardiac beta-receptors.The following investigation was, therefore, undertaken to test this thesis by acute haemodynamic studies in patients with severe hypertensive disease and to determine the clinical effectiveness of the combination of oral alpha-and beta-receptor antagonists in the longer term treatment of these patients.Patients and methodsTwelve patients with severe uncomplicated essential hypertension were studied. Five were men, average age 47 years (range 44 to 50 years) and average weight 89 kg (range 84 to 98 kg); 7 were women average age 41 years (range 34 tO 49 years) and average weight 60 kg (range 49 to 83 kg). Seven patients presented with severe headaches which had proved intractable to other antihypertensive drugs, singly or in combination. In the remainder a high blood pressure was discovered during routine medical examination for minor illnesses. The lowest diastolic pressure measured in the supine position by doctors in the ward persistently exceeded I20 mmHg (range I20 to I50) in all patients during their hospital on 12 May 2018 by guest. Protected by copyright.

Circulatory and alpha‐adrenoceptor blocking effects of phentolamine.

“…It is interesting to note that the circulating effects of oxprenolol plus phentolamine which were described by Majid et al, (1974) as being beneficial, occurred when phentolamine was being infused intravenously. Subsequent studies of chronically administered phentolamine have failed to confirm a beneficial antihypertensive effect (Johnson et al, 1976;Winchester et al, 1976).…”

“…(Majid et al, 1974). However, using the same daily dose of oral phentolamine as used by Majid et al, (1974), two other groups of investigators failed to show any enhanced reduction in blood pressure from the phentolamine over that already achieved with a P-adrenoceptor blocking drug alone (Johnson, Labrooy & Munro-Faure, 1976;Winchester Ward McKillop & Kennedy 1976).…”

“…More recently its use has been revived as an antihypertensive agent in combination with padrenoceptor blocking drugs (Majid, Meeran, Benaim, Sharma & Taylor, 1974). Its use in this context has been advocated because of its effects upon the circulation which in combination with ,B-adrenoceptor blockade provided obvious beneficial circulatory effects (Majid et al, 1974).…”

Assessment of alpha‐ and beta‐adrenoceptor blocking actions of labetalol.

“…In our study we have shown that after oral administration labetalol induced ai-adrenoceptor antagonism to phenylephrine and in addition, a fall in resting supine pressure. Majid, Meeran, Sharma & Taylor (1974) have claimed that combined a-and ,B-adrenoceptor blockade is a highly desirable pharmacological basis for the treatment of hypertensive patients. Oral labetalol possessing these combined properties is likely therefore to produce reductions in blood pressure in hypertensive patients and this has been observed in treatment of hypertension for periods up to three years (Prichard et al, 1975).…”

Hydrallazine or phentolamine as adjuncts to beta‐adrenoceptor blockade/thiazide therapy in hypertension.

“…It is also our experience that with oxprenololdiuretic regimen, in a small proportion of patients diastolic blood pressure fails to fall below levels which we have arbitrarily set at 100 mm,Hg. Majid, Meeran, Benaim, Sharma & Taylor (1974) (Galloway, Webster & Petrie, 1974) or in combination with ,B-adrenoceptor blockers (Johnson, Labrooy & Munro-Faure, 1974), however, has not been confirmed. Hydrallazine, a peripheral vasodilator, has been shown to be a useful agent in combination with a 3-adrenoceptor blocker-diuretic regimen (Aenishanslin, Pestalozzi-Kerpel, Duback, Imhof & Turri, 1972;Zacest, Gilmore & Koch-Weser, 1972).…”