Tissue protection by nifedipine and its calcium antagonistic derivatives in vascular damage

Abstract

Calcium ions are ubiquitous messengers of numerous cellular functions. Under normal conditions, they translate the membrane signal into specific cellular activity by electromechanical or electrosecretory coupling. An enhancement of the transmembrane calcium influx results in exaggerated cellular function, such as increased vascular contractility. Therefore, a reduction of transmembrane calcium influx by calcium antagonists effectively reduces high blood pressure (BP). It has been shown that the long-term treatment of genetically hypertensive rats with dihydropyridine calcium antagonists ameliorates the tissue damage that occurs in association with high BP in various organs. This tissue protection is not secondary to the reduction of hypertension as it can be demonstrated in the absence of BP reduction. This favourable effect may be attributed to the prevention of intracellular calcium overload which results in an exhaustion of energy-rich phosphates, excessive activation of proteolytic and phospholytic enzymes, membrane destruction and cellular death. In acute ischaemia experiments, inhibition of excessive transmembrane calcium influx by the dihydropyridine calcium antagonists prevents vascular and parenchymal damage. Moreover, long-term treatment with dihydropyridine calcium antagonists prevents vascular and parenchymatous damage in advanced or accelerated hypertension. In accordance with this concept, calcium antagonists have been shown to exert protective effects against acute ischaemic damage in both the heart and the kidney.