Summary
The effect of cromakalim, a K+-channel activator, on the plasma renin-angiotensin-aldosterone system, catecholamines and α-atrial natriuretic peptide, and on the intraerythrocyte concentration and transmembrane fluxes of Na+ and K+ has been investigated in 18 normal male subjects, in a double-blind parallel study. After a run-in period on placebo for 1 week, the subjects were treated either with placebo (n=6) or cromakalim (n=12) for 1 week.
Plasma renin activity was significantly increased during cromakalim. No effect of cromakalim on plasma angiotensin II, aldosterone, adrenaline, noradrenaline and α-atrial natriuretic peptide was demonstrated. The intra-erythrocyte K+ concentration was decreased during cromakalim administration and Ca2+-dependent K+-channels in red blood cells were increased.
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References
Allen SL, Boyle JP, Cortijo J, Foster RW, Morgan CP, Small RC (1986) Electrical and mechanical effects of BRL 34915 in guinea-pig isolated trachealis. Brit J Pharmacol 89: 395–405
Caviero I, Pratz J, Mondot S (1988) Cardiovascular effects of K-channel openers in vivo. In: Potassium channel modulators: New drugs with novel mechanisms of action. Conference Royal College of Physicians, Organized by IBC Technical Service, London, p 1–16
Coldwell MC, Hewlett DK (1988) Potassium efflux enhancement by cromakalim in rabbit mesenteric artery: An indirect effect independent of calcium? Biochem Pharmacol 37: 4105–4110
Cooke NS (1988) The pharmacology of potassium channels and their therapeutic potential. TIPS 9: 21–28
De Luise M, Flier JS (1985) Evidence for coordinate genetic control of Na, K-pump density in erythrocytes and leucocytes. Metabolism 34: 771–776
Ferrier S, Kurtz A, Weidmann P, Lehner P, Pusterla C, Shaw S, Saxenhofer H (1988) Stimulation of renin production by potassium-channel activation. 12th Scientific Meeting of International Society of Hypertension. Kyoto, Japan, Abstract
Fyhrquist F, Puutula L (1978) Faster radioimmunoassay of angiotensin I at 37°C. Clin Chem 24: 115–118
Hamilton TC, Weir SW, Weston AH (1986) Comparison of the effects of BRL 34915 and verapamil on electrical and mechanical activity in rat portal vein. Br J Pharmacol 88: 103–111
Hamilton TC, Weston AH (1989) Cromakalim nicorandil and pinacidil: Novel drugs which open potassium channels in smooth muscle. Gen Pharmacol 20: 1–9
Garay RP, Nazaret C, Diez J, Etienne A, Bourgan R, Braquet P (1984) Stimulation of K+-fluxes by diuretic drugs in human red cells. Biochem Pharmacol 33: 2013–2020
Garay RP, Hannaert PA, Nazaret C, Cragae EJ Jr (1986) The significance of the relative effects of loop diuretics and anti-brain edema agents on the Na+-, K+-, Cl−-cotransport system and the Cl−/NaCO −3 -anion exchanger. Naunyn-Schmiedebergs Arch Pharmacol 334: 202–209
Lijnen P, Hespel P, Lommelen G, Laermans M, M'Buyamba-Kabangu JR, Amery A (1986) Intracellular sodium, potassium and magnesium concentration, ouabain-sensitive86Rubidium-upake and sodium efflux and Na+-, K+-cotransport activity in erythrocytes of normal male subjects studied on two occasions. Methods Finds Exp Clin Pharmacol 8: 525–533
Lijnen P, Amery A, Fagard R, Katz F (1978a) Radioimmunoassay of angiotensin II in unextracted plasma. Clin Chim Acta 88: 403–412
Lijnen P, Amery A, Fagard R, Corvol P (1978b) Direct radioimmunoassay of plasma aldosterone in normal subjects. Clin Chim Acta 84: 305–314
Lijnen P, Hespel P, M'Buyamba-Kabangu JR, Goris M, Lysens R, Vanden Eynde E, Fagard R, Amery A (1988) Plasma atrial natriuretic peptide and cyclic nucleotide levels before and after a marathon. J Appl Physiol 63: 1180–1184
Malvano R, Orlandini S, Cozzani P, Duranti P, Simonini N, Salvetta A (1976) Methodological simplification in radioimmunoassay of urinary aldosterone. Clin Chim Acta 66: 331–343
Moerman EJ, De Schaepdryver AF (1984) Quantitation of catecholamines in urine and plasma. Clin Chim Acta 139: 321–333
Overlack A, Stumpe KO, Ressel C, Kolloch W, Zywzok W, Krück F (1980) Decreased urinary kallikrein activity and elevated blood pressure normalized by orally applied kallikrein in essential hypertension. Klin Wochenschr 58: 37–42
Nazaret C, Diez J, Hannaert PA, Christen MO, Wierzbicki N, Garay RP (1987) Inhibition of the Cl−-/NaCO −3 -anion exchanger by xipamide in human red blooc cells. Eur J Pharmacol 144: 353–362
Rosati C, Hannaert P, Dausse JP, Braquet P, Garay R (1986) Stimulation of beta-adrenoceptors inhibits calcium-dependent potassium channels in mouse macrophages. J Cell Physiol 129: 310–314
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Lijnen, P., Fagard, R., Staessen, J. et al. Humoral and cellular effects of the K+-channel activator cromakalim in man. Eur J Clin Pharmacol 37, 609–611 (1989). https://doi.org/10.1007/BF00562554
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DOI: https://doi.org/10.1007/BF00562554