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The effect of the calcium antagonist nifedipine on pressor and aldosterone responses to angiotensin II in normal man

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Summary

The effects of the calcium entry blocker nifedipine on blood pressure (BP) and the pressor and aldosterone responses to graded infusions of angiotensin II were studied in normal subjects using 3 protocols. Study 1 was a randomised double-blind placebo-controlled trial of nifedipine (20 mg p.o.) on supine and erect BP in 9 subjects. There was a highly significant fall in BP: (8±4 mmHg; mean±SDM;p<0.001) with maximum changes occurring 30 min after drug administration. Significant reciprocal changes in pulse rate were observed. These changes were not altered by prior administration of the prostaglandin synthetase inhibitor flurbiprofen (100 mg). In Study 2, 6 subjects were given nifedipine (20 mg) or no treatment mid-way between 2 identical graded infusions of angiotensin II (5, 10 and 20 ng/kg/min) separated by an interval of 1 h on each of 2 study days, and blood pressure and aldosterone responses were measured. There was a significant attenuation of both pressor (p<0.05) and aldosterone (p<0.05) responses. The changes in aldosterone responses were not due to changes in plasma renin, potassium or adrenocorticotrophin. In study 3 the pressor and aldosterone responses to angiotensin II (2, 5, 10 and 20 ng/kg/min) were studied after 3 days treatment with nifedipine (20 mg thrice daily) or placebo. Pressor dose response curves to both angiotensin II and noradrenaline were shifted in parallel to the right, but not significantly, and aldosterone responses to angiotensin II were unchanged by nifedipine. These results show that nifedipine may decrease BP in normal subjects by decreasing pressor and aldosterone responses to angiotensin II and that the aldosterone response to angiotensin II in man is possibly calcium-dependent.

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Millar, J.A., McLean, K.A., Sumner, D.J. et al. The effect of the calcium antagonist nifedipine on pressor and aldosterone responses to angiotensin II in normal man. Eur J Clin Pharmacol 24, 315–321 (1983). https://doi.org/10.1007/BF00610047

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Key words

  • aldosterone
  • flurbiprofen
  • nifedipine
  • blood pressure
  • calcium flux
  • prostaglandins