Role of Intracellular Calcium in the Regulation of Renal Hemodynamics
Intracellular calcium contributes to renal hemodynamic regulatory mechanisms in multiple ways. Calcium channel blockers elicit a selective vasodilation of preglomerular arterioles leading to increases in renal blood flow (RBF), glomerular filtration rate (GFR), and glomerular pressure, with marked attenuation of autoregulatory capability. The effects of these agents seem to be restricted to the component of renal vascular resistance responsible for autoregulation and contrast with other agents which vasodilate the kidney at arterial pressures below, as well as within, the auto-regulatory range. This component of renal vascular resistance that is not influenced by calcium entry blockade can be altered by angiotensin converting enzyme inhibition. Studies at the microvascular level have demonstrated that the effects of angiotensin II on afferent arterioles are dependent upon calcium entry whereas the vasoconstrictor actions on efferent arterioles are not influenced by calcium channel blockade. The macula densa cells responsible for mediating tubular glomerular feedback (TGF) appears to utilize a different type of intracellular calcium mechanism for transmission of feedback signals. Increases in the intralumenal solute concentration at the macula densa elicit feedback signals to constrict the afferent arterioles and reduce glomerular pressure. These effects can be artificially induced by the intralumenal addition of calcium ionophores; however, intralumenal addition of calcium channel blockers or variation in intralumenal calcium concentration do not interfere with signal transmission. In contrast, agents that interfere with intracellular calcium mobilization can block TGF responses. Thus, intracellular mobilization of cytosolic calcium within the macula densa cells leads to transmission of TGF signals to the vascular cells. At the afferent arteriolar effector site, transmembrane calcium flux appears to serve as the dominant mechanism for regulating intracellular calcium, since TGF-mediated vasoconstrictor responses are abolished by calcium channel blockade. The efferent arterioles may be less responsive to TGF signals because of their relative insensitivity to agents that alter transmembrane calcium flux.
KeywordsCalcium Channel Blocker Renal Blood Flow Cytosolic Calcium Renal Vascular Resistance Afferent Arteriole
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- 4.Loutzenhiser R, Leyten P, Saida K, Van Breemen C (1985) Calcium compartments and mobilization during contraction of smooth muscle. In: Graver AK, Daniel EE (eds) Calcium and contractility. Humona, pp 61–92Google Scholar
- 5.Chomdej B, Bell PD, Navar LG (1977) Renal hemodynamic and autoregulatory responses to acute hypercalcemia. Am J Physiol (Renal Fluid Electrolyte Physiol 6) 232: F490 - F496Google Scholar
- 12.Mitchell KD, Navar LG (1990) Tubuloglomerular feedback responses during peritubular infusions of calcium channel blockers. Am J Physiol (Renal Fluid Electrolyte Physiol 27) 258: F537 - F544Google Scholar
- 14.Carmines PK, Navar LG (1989) Disparate effects of Ca channel blockade on afferent and efferent arteriolar responses to ANG II. Am J Physiol (Renal Fluid Electrolyte Physiol 25) 256: F1015 - F1020Google Scholar
- 15.Casellas D, Navar LG (1984) In vitro perfusion of juxtamedullary nephrons in rats. Am J Physiol (Renal Fluid Electrolyte Physiol 15) 246: F349 - F358Google Scholar
- 16.Steinhausen M, Baehr M (1989) Vasomotion and vasoconstriction induced by a Cat’-antagonist in the split hydronephrotic kidney. Prog Appl Microcirc 14: 25–39Google Scholar
- 18.Lafferty HM, Gunning M, Brady HR, Brenner BM, Anderson S (1990) Renal hemodynamic and natriuretic effects of manganese and interactions with atrial natriuretic peptide. Am J Physiol (Renal Fluid Electrolyte Physiol 27) 258: F998 - F1004Google Scholar
- 19.Smith JB (1986) Angiotensin-receptor signaling in cultured vascular smooth muscle cells. Am J Physiol (Renal Fluid Electrolyte Physiol 19) 250: F759 - F769Google Scholar
- 21.Bell PD, Navar LG (1982) Macula densa feedback control of glomerular filtration: Role of cytosolic calcium. Miner Electrolyte Metab 8: 61–77Google Scholar
- 28.Bell PD, Franco-Guevara M, Abrahamson DR, Lapointe JY, Cardinal J (1988) Cellular mechanism for tubuloglomerular feedback signalling. In: Persson AEG, Boberg U (eds) The juxtaglomerular apparatus. Elsevier, Amsterdam, pp 63–77Google Scholar