Experimental Pharmacology of Nisoldipine: Perspectives from Long-Term Studies

  • S. Kazda
  • J.-P. Stasch
  • Claudia Hirth
Conference paper


Nisoldipine is a 1,4-dihydropyridine derivative with an outstanding vascular selectivity. As a specific calcium antagonist, it shortens the action potential and causes electromechanical uncoupling in ventricular myocardium. However, this effect, resulting in a negative inotropic action, appears at 100–1000 times higher concentrations of nisoldipine in comparison with its inhibition of calcium-dependent vascular contractions. Detailed analyses of pharmacological effects revealed additional properties such as enhancement of sodium excretion, an interaction with the reninangiotensin-aldosterone system and a protective effect against acute renal ischaemia, that may contribute to its therapeutic efficacy.

In chronic experiments nisoldipine prevented mortality, reduced cardiac hypertrophy and limited vascular lesions, normalising blood pressure in prophylactic administration to spontaneously hypertensive rats as well as in therapeutic administration to Dahl rats with already existing malignant hypertension. It is evident that such effects cannot be achieved by a simple peripheral vasodilation.

In fact, minoxidil only temporarily decreased blood pressure in Dahl rats with malignant hypertension; the degree of cardiac hypertrophy was even aggravated by minoxidil. Some additional effect of nisoldipine normalising water and electrolyte balance by an improvement of the impaired kidney function, is postulated. In addition, nisoldipine induced a regression of cardiac hypertrophy and improved survival rate when given therapeutically to old, spontaneously hypertensive rats with evident heart failure. Simultaneously, this drug induced a decrease of high plasma levels of atrial natriuretic peptides (ANP) in these rats. The mechanism of the therapeutic effect of nisoldipine is complex. It involves a decrease of the total peripheral vascular resistance (reduction of afterload) and an increase in coronary blood flow. Moreover, nisoldipine obviously normalises the impaired volume homoeostasis by improving renal function and thus reduces the need for activation of the ANP system.

In the advanced stages of hypertension, nisoldipine prevents deleterious calcium overload and the resulting tissue damage.


Cardiac Hypertrophy Atrial Natriuretic Peptldes Total Peripheral Vascular Resistance Negative Inotropic Action Cardiac Purkinje Fiber 
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Copyright information

© Springer-Verlag Berlin Heidelberg 1987

Authors and Affiliations

  • S. Kazda
  • J.-P. Stasch
  • Claudia Hirth

There are no affiliations available

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