Guanethidine-Resistant Hypertension

Resistance of hypertensive patients to large doses of guanethidine is seldom due to defective absorption of the drug, since the existence of adrenergic blockade can be demonstrated in these cases.The effect on the blood pressure of intravenous phenoxybenzamine and norepinephrine, respectively, has been compared in groups of hypertensive patients resistant and responsive to guanethidine.As both the hypotensive action of intravenous phenoxybenzamine, a peripheral antagonist of norepinephrine, and the pressor effect of norepinephrine infusion were more marked in patients resistant to guanethidine it seems likely that the maintenance of high blood pressure in these cases is due to enhanced sensitivity of the arterioles to endogenous norepinephrine. To combat this effect the therapeutic use of phenoxybenzamine appeared logical.Phenoxybenzamine taken by mouth has been found by itself to be an unsatisfactory hypotensive agent but when used in combination with guanethidine has proved highly effective. The blood pressure of 13 out of 16 hypertensive cases previously resistant to guanethidine in high dosage has been controlled for periods of from 3 to 30 months after the addition of phenoxybenzamine.When used in combination with guanethidine, phenoxybenzamine caused no side effects.