1. The new peripherally acting selective 5-hydroxytryptamine receptor blocking agent ketanserin was given (10 mg intravenously) to 17 patients with essential hypertension.

2. Systemic mean systolic arterial pressure fell from 192 ± 6 to 146 ± sem 10 mmHg and mean diastolic arterial pressure fell from 90 ± 4 to 68 ± 5 mmHg. Right atrial pressure, pulmonary arterial pressure and pulmonary capillary ‘wedge’ pressure, measured in 12 patients, were also significantly lowered. Heart rate, cardiac output and plasma noradrenaline rose after ketanserin, probably due to baroreflex-mediated sympathetic stimulation, but the changes were small compared with the fall in systemic arterial pressure.

3. Phenylephrine (50, 100 and 200 μg intravenously) was given to five patients before ketanserin and during continuous infusion of ketanserin (2 mg/h after a loading dose of 10 mg) and dose-response curves for mean systemic arterial pressure were constructed. The pressor response to phenylephrine was not shifted by ketanserin. Thus ketanserin, in a dose capable of lowering systemic arterial pressure, does not act as an α-adrenoceptor antagonist.

4. 5-Hydroxytryptamine receptor blockade appears to cause dilatation of resistance vessels and possibly also of capacitance vessels. The data suggest a hitherto unknown role for 5-hydroxytryptamine in the maintenance of high blood pressure.

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