GUANETHIDINE AND METHYLDOPA: A HAeMODYNAMIC STUDY

Abstract

Guanethidine and methyldopa are commonly used drugs in the treatment of hypertension, but the manner in which they act on the circulation to lower the blood pressure remains controversial. Systemic arterial pressure depends on both cardiac output and total peripheral resistance, and a reduction in either of these can result in a fall of pressure. Guanethidine has been said by some to act principally by lowering peripheral resistance (Lichtlen, Schaub, and Biihlmann, 1960;Roy, Mathur, and Bhatia, 1961;Taylor et al., 1962), while others have considered a fall in cardiac output to be the most important factor (Richardson et al., 1960;Rokseth et al., 1962). Dollery, EmslieSmith, and Shillingford (1961) thought the postural hypotensive effect was to some extent due to a failure of vasoconstriction to compensate for the normal reduction in cardiac output on standing.There is a similar lack of agreement about the action of methyldopa. Sannerstedt, Varnauskas, and Werko (1962) reported a dominant action on peripheral resistance, whereas Wilson, Fisher, and Kirkendall (1962) noted a fall in cardiac output with no significant change in peripheral resistance. Onesti et al. (1962) and Dollery, Harington, and Hodge (1963) found a reduction in both peripheral resistance and cardiac output in most of the patients they studied.There are several reasons for the apparent disparity in the results obtained by different workers. First, in some series, observations were made with subjects supine, and are of limited value in investigating the action of drugs that produce their greatest effect with patients in the upright position. Secondly, most hiemodynamic studies were of the acute effects of the drugs given intravenously: their pharmacology is complicated, and the results may not be comparable to those obtained in investigations of the long-term action of orally administered drugs. Thirdly, the response of patients in heart failure to hypotensive agents is peculiar in that a fall in atrial filling pressure resulting from venous pooling may increase cardiac output (Freis et al., 1953): data obtained from a study of patients with raised venous pressure are therefore not applicable to those in whom it is normal. Finally, there is almost certainly more than one mechanism by which guanethidine and methyldopa reduce blood pressure, and the pattern of response may vary from patient to patient.In this paper, we report the effects on blood pressure, heart rate, and cardiac output of routine treatment of hypertensive patients with oral guanethidine and methyldopa. We have made our observations with the patients supine, propped upright, and walking, both before treatment and after stabilization. We have, therefore, collected our data under conditions that are as relevant as possible to the normal management of hypertension. PATIENTS AND METHODSFifteen patients with a diagnosis of essential hypertension (9 men and 6 women, whose ages ranged from 36 to 71 years) agreed to take part in this study. None had any history of frank heart failure, al...

The Effect of Guanethidine and Propranolol on Capillary Blood Flow in Subcutaneous Tissue and Muscle in Essential Hypertension

“…This finding is in general agreement with reports which suggest inhibition of sympathetic vasoconstrictor mechanisms by guanethidine [1,4] and sub sequent decrease in total peripheral vascular resistance in hypertensive subjects [4,12,13,23], It would appear, however, that this vasomotor effect is not generalized, since guanethidine causes a simultaneous reduc tion in capillary flow in forearm muscle. The fact that guanethidine practi cally eliminated the differences between untreated hypertensives and healthy controls suggests that the hemodynamic pattern of hypertension involves an increased sympathetic tone which is 'neutralized' by guanethidine with a return to a normal distribution pattern of local tissue blood flows.…”

THE USE OF RADIOACTIVE MICROSPHERES TO COMPARE THE EFFECTS OF HYDRALAZINE, GUANETHIDINE AND SK&F 24260 ON THE REDISTRIBUTION OF CARDIAC OUTPUT IN ANAESTHETIZED RABBITS

“…Fielden & Green (1967) concluded that guanethidine also had a strong adrenergic neurone blocking action distinct from the depleting action. It has been suggested that a reduction in total peripheral resistance (by blocking the sympathetic nervous system) is the mechanism by which guanethidine lowers blood pressure (Chamberlain & Howard, 1964). In the present experiments the total peripheral conductance was only increased by 17% after guanethidine; there was no significant change in any individual organ.…”

Antihypertensive Effect of Diuretics

“…It could be argued that the diuresis causes a fall in cardiac output, and with time this could result, by some undefined means, in a fall in peripheral resistance. Something similar to this has in fact been reported after propranolol therapy (TARAZI et aI., 1972) and there is also some evidence that it occurs with long-term treatment with guanethidine (VILLARREAL et at, 1964, CHAMBERLAIN andHOWARD, 1964). That vague constellation of ideas which surrounds "resetting of baroreceptors" should be mentioned here, although the term has been debased beyond any useful meaning.…”