Functional Importance of L- and P/Q-Type Voltage-Gated Calcium Channels in Human Renal Vasculature

Abstract

Abstract-Calcium channel blockers are widely used for treatment of hypertension, because they decrease peripheral vascular resistance through inhibition of voltage-gated calcium channels. Ϫ8 mol/L. The T-type antagonist mibefradil inhibited the potassium-induced constriction with large variations between patients. Interestingly, the P/Q-type antagonist, -agatoxin IVA, inhibited significantly the contraction with 24% at 10 Ϫ9 mol/L. In conclusion L-, P/Q, and T-type channels are expressed in human renal blood vessels, and L-and P/Q-type channels are of functional importance for the depolarization-induced vasoconstriction. The contribution of P/Q-type channels to contraction in the human vasculature is a novel mechanism for the regulation of renal blood flow and suggests that clinical treatment with calcium blockers might affect vascular reactivity also through P/Q-type channel inhibition.

Differential effect of T-type voltage-gated Ca2+ channel disruption on renal plasma flow and glomerular filtration rate in vivo

“…Renal blood vessels were isolated from patients who underwent nephrectomy for renal cancer and had given their informed written consent. Kidneys were extirpated, and intrarenal arteries (interlobar and arcuate arteries) were isolated from normal tissue (18). The study included 13 patients, with the primary diagnoses being either malign or benign tumours.…”

“…Human intrarenal arteries were isolated under a stereomicroscope and stored at 4°C until the next day in the following solution (in mmol/l): 103 NaCl, 5.4 KCl, 4.0 NaHCO 3, 1.5 NaH2PO4, 0.8 MgSO4, 5.1 glucose, 0.9 Na-pyruvate, 30 Na-isethionic acid, and 5.6 HEPES 5.6 with added 10 ml/l MEM vitamin solution (M6895, Sigma), 20 ml/l MEM essential amino acid solution (M5550, Sigma), and 10 ml/l MEM nonessential amino acid solution (M7145, Sigma) (18). Human intrarenal arteries were mounted in a Halpern-Mulvany wire myograph (model 610, Danish Myo Technology, Aarhus, Denmark), and isometric force development was measured (PowerLab, AD Instruments, Colorado Springs, CO).…”

Functional importance of T-type voltage-gated calcium channels in the cardiovascular and renal system: news from the world of knockout mice

“…Thus, contraction induced by pressure and many vasoactive agonists involves voltage-gated calcium channels. Several types of calcium channels, including T-type channels, might be involved in the excitation-contraction mechanism in the blood vessels of both rodents and humans (1,5,33,34,72). Therefore, T-type channels may contribute to the regulation of peripheral vascular resistance.…”

“…Two T-type channel molecular subtypes (Ca v 3.1 and Ca v 3.2) have been identified by molecular techniques in the rat renal (33), rat and mouse mesenteric (5, 9, 30), brain (57,72), and rat cremaster arteries (108). Both Ca v 3.1 and Ca v 3.2 channels are expressed in rat, mouse, and human vascular smooth muscle cells (19,34,98). Furthermore, Ca v 3.3 has been identified in dog basilar arteries (73).…”

“…The mesenteric vessels were mounted in a perfusion set-up, as previously described (90), and changes in luminal diameter were tested in response to increasing concentrations of phenylephrine. Both the intrarenal arteries and mesenteric arteries were mounted on a wire myograph (34), and concentration-dependent responses to the ␣ 1 -adrenergic receptor agonist, phenylephrine, were tested. The results revealed significant effects of Ca v 3.1 channels on vascular responses.…”