Abstract
Ketanserin (120 mg/day) or placebo was given orally to 14 patients with mild to moderate essential hypertension according to a double blind crossover protocol, each treatment period lasting six weeks. Resting intra-arterial pressure in the recumbent position was reduced from 150/84 to 141/77 mm Hg; the hypotensive effect persisted throughout an uninterrupted graded exercise test to the point of exhaustion. The haemodynamic effects were similar at rest and during exercise. Overall, systemic vascular resistance decreased by 14%, heart rate fell by 5%, but stroke volume and cardiac output increased. Mean pulmonary arterial pressure and capillary wedge pressure were not significantly affected, but pulmonary vascular resistance decreased by 15%. The pressor response to methoxamine was significantly reduced by ketanserin. Both plasma noradrenaline and adrenaline concentrations increased, plasma renin activity and angiotensin II concentration decreased, and plasma aldosterone concentration was unchanged. The data indicate that ketanserin induces arteriolar dilatation, possibly related to an alpha-1-antagonistic action and to a reduced circulating angiotensin II concentration. The haemodynamic response is complex, and an increase in cardiac output limits the hypotensive effect. There is no firm evidence of an effect on venous tone as cardiac filling pressures do not change.
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- Da Prada M., Zürcher Simultaneous radioenzymatic determination of plasma and tissue adrenaline, noradrenaline and dopamine within the femtomole range. Life Sci. 1976 Oct 15;19(8):1161–1174. doi: 10.1016/0024-3205(76)90251-4. [DOI] [PubMed] [Google Scholar]
- De Cree J., Verhaegen H., Symoens J. Acute blood-pressure-lowering effect of ketanserin. Lancet. 1981 May 23;1(8230):1161–1162. doi: 10.1016/s0140-6736(81)92331-x. [DOI] [PubMed] [Google Scholar]
- Demoulin J. C., Bertholet M., Soumagne D., David J. L., Kulbertus H. E. 5-HT2-receptor blockade in the treatment of heart failure. A preliminary study. Lancet. 1981 May 30;1(8231):1186–1188. doi: 10.1016/s0140-6736(81)92352-7. [DOI] [PubMed] [Google Scholar]
- Fozard J. R. Mechanism of the hypotensive effect of ketanserin. J Cardiovasc Pharmacol. 1982 Sep-Oct;4(5):829–838. doi: 10.1097/00005344-198209000-00020. [DOI] [PubMed] [Google Scholar]
- Fyhrquist F., Puutula L. Faster radioimmunoassay of angiotensin I at 37 degrees C. Clin Chem. 1978 Jan;24(1):115–118. [PubMed] [Google Scholar]
- Is ketanserin a D receptor antagonist? Lancet. 1983 Mar 26;1(8326 Pt 1):703–704. [PubMed] [Google Scholar]
- Kalkman H. O., Timmermans P. B., Van Zwieten P. A. Characterization of the antihypertensive properties of ketanserin (R 41 468) in rats. J Pharmacol Exp Ther. 1982 Jul;222(1):227–231. [PubMed] [Google Scholar]
- Leysen J. E., Awouters F., Kennis L., Laduron P. M., Vandenberk J., Janssen P. A. Receptor binding profile of R 41 468, a novel antagonist at 5-HT2 receptors. Life Sci. 1981 Mar 2;28(9):1015–1022. doi: 10.1016/0024-3205(81)90747-5. [DOI] [PubMed] [Google Scholar]
- Lijnen P. J., Amery A. K., Fagard R. H., Katz F. H. Radioimmunoassay of angiotensin II in unextracted plasma. Clin Chim Acta. 1978 Sep 1;88(2):403–412. doi: 10.1016/0009-8981(78)90447-3. [DOI] [PubMed] [Google Scholar]
- Lijnen P., Amery A., Fagard R., Corvol P. Direct radioimmunoassay of plasma aldosterone in normal subjects. Clin Chim Acta. 1978 Mar 15;84(3):305–314. doi: 10.1016/0009-8981(78)90246-2. [DOI] [PubMed] [Google Scholar]
- NISHITH S. D., DAVIS L. D., YOUMANS W. B. Cardioaccelerator action of angiotensin. Am J Physiol. 1962 Feb;202:237–240. doi: 10.1152/ajplegacy.1962.202.2.237. [DOI] [PubMed] [Google Scholar]
- Oparil S., Haber E. The renin-angiotensin system (first of two parts). N Engl J Med. 1974 Aug 22;291(8):389–401. doi: 10.1056/NEJM197408222910805. [DOI] [PubMed] [Google Scholar]
- Persson B., Hedner T., Henning M. Cardiovascular effects in the rat of ketanserin, a novel 5-hydroxytryptamine receptor blocking agent. J Pharm Pharmacol. 1982 Jul;34(7):442–445. doi: 10.1111/j.2042-7158.1982.tb04753.x. [DOI] [PubMed] [Google Scholar]
- Stranden E., Roald O. K., Krohg K. Treatment of Raynaud's phenomenon with the 5-HT2-receptor antagonist ketanserin. Br Med J (Clin Res Ed) 1982 Oct 16;285(6348):1069–1071. doi: 10.1136/bmj.285.6348.1069. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tait S. A., Tait J. F., Bradley J. E. The effect of serotonin and potassium on corticosterone and aldosterone production by isolated zona glomerulosa cells of the rat adrenal cortex. Aust J Exp Biol Med Sci. 1972 Dec;50(7):833–846. doi: 10.1038/icb.1972.81. [DOI] [PubMed] [Google Scholar]
- Van Nueten J. M., Janssen P. A., Van Beek J., Xhonneux R., Verbeuren T. J., Vanhoutte P. M. Vascular effects of ketanserin (R 41 468), a novel antagonist of 5-HT2 serotonergic receptors. J Pharmacol Exp Ther. 1981 Jul;218(1):217–230. [PubMed] [Google Scholar]
- Wenting G. J., Man in 't Veld A. J., Woittiez A. J., Boomsma F., Schalekamp M. A. Treatment of hypertension with ketanserin, a new selective 5-HT2 receptor antagonist. Br Med J (Clin Res Ed) 1982 Feb 20;284(6315):537–539. doi: 10.1136/bmj.284.6315.537. [DOI] [PMC free article] [PubMed] [Google Scholar]
- de Roose J., Symoens J. Ketanserin in acute superficial thrombophlebitis. Lancet. 1982 Aug 21;2(8295):440–441. doi: 10.1016/s0140-6736(82)90469-x. [DOI] [PubMed] [Google Scholar]