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A comparison of the haemodynamic and hormonal effects of low and conventional dose cyclopenthiazide in normal volunteers

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Summary

In this study we compared low (125 μg) and conventional (500 μg) doses of cyclopenthiazide on the renin angiotensin system, plasma and extracellular fluid volumes and the pressor responsiveness to angiotensin II since we have previously shown that the two doses have the same antihypertensive effect but different effects on plasma renin activity.

Following a two week placebo run-in period, 8 healthy male volunteers received 125 μg or 500 μg of cyclopenthiazide for 2 treatment periods of 4 weeks as part of a double blind, 2-part crossover study with treatment periods separated by a 4-week placebo washout phase. Measurements were made on two study days at the beginning and end of the active treatment periods. On the first day serum potassium, plasma renin activity and plasma angiotensin II levels were measured after a 1 h period of supine rest. Plasma and extracellular fluid volumes were also measured after appropriate equilibration times. The blood pressure responses to angiotensin II were assessed on day 2.

The 500 μg dose of cyclopenthiazide had a greater effect than the 125 μg dose on plasma renin activity, serum potassium, angiotensin II levels and extracellular fluid volumes. Neither drug had any effect on plasma volume or the responsiveness to infused angiotensin II.

Low dose cyclopenthiazide failed to increase angiotensin II levels, contract body fluid volumes or attenuate vascular reactivity in normotensive volunteers.

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References

  • Boer P (1984) Estimated lean body mass as an index for normalisation of body fluid volumes in humans. Am J Physiol 247: F632-F636

    Google Scholar 

  • Bourgoignie JJ, Cantanzaro RJ, Perry HMF (1968) Renin-angiotensin-aldosterone system during chronic thiazide therapy of benign hypertension. Circulation 37: 27–35

    Google Scholar 

  • Campbell DJ (1987) Circulating and tissue angiotensin systems. J Clin Invest 79: 1–6

    Google Scholar 

  • Catt KJ, Zimmet PZ, Cain MD, Cran E, Best JB, Coghlan JP (1971) Angiotensin II blood levels in human hypertension. Lancet I: 459–464

    Google Scholar 

  • Chinn RH, Dusterdieck G (1972) The response of blood pressure to infusion of angiotensin II: Relation to plasma concentrations of renin and angiotensin II. Clin Sci 42: 489–504

    Google Scholar 

  • Ferris TF (1982) The kidney and hypertension. Arch Intern Med 142: 1889–1895

    Google Scholar 

  • Fries ED (1983) How diuretics lower blood pressure? Am Heart J 106 (1 part 2): 185–187

    Google Scholar 

  • Fruncillo RJ, Rotmensch HH, Vlasses PH, Koplin JR, Swanson BW, Ferguson RK (1985) Response to captopril and hydrochlorothiazide on the response to pressor agents in hypertensives. Eur J Clin Pharmacol 28: 5–9

    Google Scholar 

  • Haber E, Koerner T, Page LB, Kliman B, Purnode A (1969) Application of a radioimmunoassay for angiotensin I to the physiologic measurements of plasma renin activity in normal subjects. J Clin Endocrinol 29: 1349–1355

    Google Scholar 

  • Hills M, Armitage P (1979) The two-period cross-over clinical trial. Br J Clin Pharmacol 8: 7–20

    Google Scholar 

  • Hollenberg NK, Chenitz WR, Adams DF, Williams GH (1974) Reciprocal influence of salt intake on adrenal glomerulosa and renal vascular responses to angiotensin II in normal man. J Clin Invest 54: 34–42

    Google Scholar 

  • Ibsen H, Leth A, Hollnagel H, Kappelgaard AM, Damkjaer Nielsen M, Giese JW (1978) Renin-angiotensin system in mild essential hypertension. The functional significance of angiotensin II in untreated and thiazide treated hypertensive patients. Clin Sci Mol Med 55: 319S-321S

    Google Scholar 

  • Johnston CI (1976) Effect of antihypertensive drugs on the renin angiotensin system. Drugs 12: 274–291

    Google Scholar 

  • Kaplan N, Silah JG (1964) The effect of angiotensin on the blood pressure in humans with hypertensive disease. J Clin Invest 43: 659–669

    Google Scholar 

  • Krstulovic AM, Dziedzic SW, Bertani-Dziedzic L, Dirico DE (1981) Plasma catecholamines in hypertension and phaeochromocytoma determined using non-pair reversed-phase chromatography with amperometric detection. Investigation of separation mechanism and clinical methodology. J Chromatogr 217: 523–537

    Google Scholar 

  • Laragh JH (1973) Vasoconstriction-volume analysis for understanding and treating hypertension: the use of renin and aldosterone profiles. Am J Med 55: 261–274

    Google Scholar 

  • Lauwers P, Conway J (1960) Effect of long-term treatment with chlorothiazide on body fluids, serum electrolytes, and exchangeable sodium in hypertensive patients. J Lab Clin Med 56: 401–408

    Google Scholar 

  • Leth A (1970) Changes in plasma and extracellular fluid volume in patients with essential hypertension during long term treatment with hydrochlorothiazide. Circulation 42: 479–485

    Google Scholar 

  • McVeigh G, Galloway D, Johnston GD (1988) The case for low dose diuretics in hypertension: comparison of low and conventional dose of cyclopenthiazide. Br Med J 297: 95–98

    Google Scholar 

  • Melby JC (1986) The renin-angiotensin-aldosterone complex. Am J Med 81 [Suppl 4C]: 9–12

    Google Scholar 

  • Negus P, Tammen L, Dunn MJ (1976) Indomethacin potentiates the vasoconstrictor actions of angiotensin II in normal man. Prostaglandins 12: 175–180

    Google Scholar 

  • Nussberger J, Re R, Matsueda GR, Haber E (1984) A simplified radioimmunoassay for physiologically active angiotensin peptides (1–8) octa- and (2–8) heptapeptides. Horm Metab Res 16: 606–610

    Google Scholar 

  • Paller MS, Douglas JG, Linas SL (1984) Mechanism of decreased vascular reactivity to angiotensin II in conscious, potassium deficient rats. J Clin Invest 73: 79–86

    Google Scholar 

  • Struyker-Boudier HAJ, Smits JFM, Kleinjans JCS, Van Essen H (1983) Hemodynamic actions of diuretic agents. Clin Exper Hypertens A5 (Part 2): 209–223

    Google Scholar 

  • Sumner DJ, Elliott HL (1987) The pressor dose response in clinical cardiovascular pharmacology. Br J Clin Pharmacol 23: 499–503

    Google Scholar 

  • Swales JD, Thurston H (1977) Plasma renin and angiotensin II measurement in hypertensive and normal subjects: correlation of basal and stimulated states. J Clin Endocrinol Metab 45: 159–163

    Google Scholar 

  • Swart S, Bing RF, Swales JD, Thurston H (1982) Plasma renin in long-term diuretic treatment of hypertension: effect of discontinuing and restarting therapy. Clin Sci 63: 121–125

    Google Scholar 

  • Tarazi RC, Frohlich ED, Dustan HP (1968) Plasma volume in men with essential hypertension. N Engl J Med 278: 762–765

    Google Scholar 

  • Thurston H, Laragh J (1975) Prior receptor occupancy as a determinant of pressor activity of infused angiotensin II in the rat. Circ Res 36: 113–117

    Google Scholar 

  • Weinberger MH, Ramsdell JW, Rosner DR, Geddes JJL (1972) Effect of chlorothiazide and sodium on vascular responsiveness to angiotensin II. Am J Physiol 223 (5): 1049–1052

    Google Scholar 

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McVeigh, G.E., McMaster, M., Linton, T. et al. A comparison of the haemodynamic and hormonal effects of low and conventional dose cyclopenthiazide in normal volunteers. Eur J Clin Pharmacol 38, 351–357 (1990). https://doi.org/10.1007/BF00315574

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