Effects of calcium antagonists on renal hemodynamics and glomerular function

Cytosolic [Ca²⁺] can be increased by influx of the ion from the extracellular compartment, Ca²⁺ release from intracellular storage sites, and/or a reduced activity of active transport processes for Ca²⁺ extrusion or sequestration. Organic calcium antagonists block transmembrane calcium entry and, therefore, can be utilized to evaluate the importance of calcium influx in the regulation of renal hemodynamics. Recent studies indicate that calcium antagonists selectively vasodilate preglomerular arterioles, leading to increases in renal blood flow (RBF), glomerular filtration rate (GFR) and glomerular pressure. In contrast with angiotensin converting enzyme inhibitors and other vasodilator aeents, calcium antagonists primarily influence the component of renal vascular resistance responsible for autoregulation, potently attenuating autoregulatory efficiency. Calcium antagonists also block the afferent arteriolar vasoconstriction elicited by angiotensin II, while not influencing the efferent arteriolar vasoconstriction evoked by this peptide. Tubuloglomerular feedback (TGF)-mediated vasoconstrictor responses are also abolished by calcium antagonists, indicating that the TGF effector mechanism may require transmembrane calcium influx into the smooth muscle cells of the afferent arterioles. These observations provide compelling evidence that calcium influx, through pathways which are influenced by organic calcium antagonists, is an integral component of the afferent arteriolar vasoconstriction elicited by a variety of stimuli, while efferent arteriolar vasoconstriction appears to depend on other calcium access pathways.