Effects of L-Type Calcium Channel Activation on Renal Vascular Resistances in the Lyon Hypertensive Rat

Abstract

This study aimed to evaluate the role of L-type calcium channels in the increased renal vascular resistance (RVR) of the Lyon hypertensive (LH) rat before and after normalization of its blood pressure (BP) by angiotensin-converting enzyme inhibition with perindopril. Concentration-response curves to Bay K 8644 (from 0.1 nM to 1 microM), a selective agonist of L-type calcium channels, were obtained in single-pass perfused kidneys isolated from groups of eight untreated or perindopril-treated (3 mg/kg/day, p.o., from age 3 to 7 weeks) LH and low-BP (LL) control rats. In untreated rats, the negative logarithm of the molar concentration of Bay K 8644 required to produce a half-maximal effect (pD2) values for Bay K 8644 did not differ between the two strains, whereas the maximal RVR response was higher in LH than in LL kidneys (28.0+/-4.9 vs. 12.9+/-0.8 mm Hg/ml/min/g, respectively). Perindopril normalized BP and RVR in LH rats and suppressed the interstrain differences in the maximal RVR responses (11.4+/-0.6 vs. 10.5+/-1.2 mm Hg/ml/min/g in LH and LL rats, respectively). These results demonstrate that LH rats exhibit an increased maximal contractile response to Bay K 8644 compared with LL controls, and that this alteration is not a primary defect because it disappears after normalization of BP level.

Y27632, a Rho‐activated kinase inhibitor, normalizes dysregulation in alpha1‐adrenergic receptor‐induced contraction of Lyon hypertensive rat artery smooth muscle

“…Ca 2+ permeability appears to be greater in LH SMA, compared with LN SMA. An L‐type Ca 2+ channel is unlikely involved in the reduction of Ca 2+ influx, because L‐type channels are upregulated in LH [7] as well as in spontaneously hypertensive rat basilar artery [16]. Because the deficiency in the Ca 2+ influx is normalized by the treatment with Y27632, this suggests an involvement of ROK.…”

“…Enhanced constriction of small caliber resistance arteries and arterioles causes an increase in peripheral vascular resistance of LH rats, which is an important component of human essential hypertension and other animal models of hypertension [5]. Several abnormalities of Ca 2+ handling have been found in LH such as increased cellular Ca 2+ levels in platelets and erythrocytes [6] and an enhanced responsiveness of renal circulation to dihydropyridine L‐type Ca 2+ channel openers and blockers [7]. However, little is known about the possible dysregulation of smooth muscle contraction in LH arteries.…”