Ca2+ sensitization and Ca2+ entry in the control of blood pressure and adrenergic vasoconstriction in conscious Wistar–Kyoto and spontaneously hypertensive rats

Abstract

Ca sensitization mediated by RhoA/Rho kinase pathway is attenuated in SHR compared with normotensive WKY rats. This might be a part of the compensation for enhanced Ca entry through L-VDCC in genetic hypertension.

Ontogenetic changes in contribution of calcium sensitization and calcium entry to blood pressure maintenance of Wistar–Kyoto and spontaneously hypertensive rats

“…Most of the drugs were dissolved in physiological saline, but nifedipine was dissolved in DMSO [13]. The drugs were usually given as an intravenous bolus (1 ml/kg).…”

“…The experiments were carried out in conscious rats kept in small transparent cages [13]. BP was measured using PowerLab system (ADInstruments Ltd, Bella Vista, NSW, Australia) between 0800 and 1130 h to reduce circadian variations in BP levels.…”

“…The role of enhanced calcium entry through L-type voltagedependent calcium channels (L-VDCCs) in genetic hypertension is well known [6][7][8][9], but less attention has been paid to the changes of calcium sensitization (mediated by RhoA/Rho kinase pathway) in spontaneously hypertensive rats (SHRs) [10][11][12]. Recently, we have demonstrated that basal calcium sensitization [determined in animals subjected to a blockade of major pressor systems -sympathetic nervous system (SNS) and renin-angiotensin system (RAS)] is decreased in adult SHR compared with Wistar-Kyoto (WKY) controls [13]. On the contrary, blood pressure (BP) response to the acute Rho kinase inhibition by fasudil or Y-27632 was found to be enhanced in SHR with intact SNS and RAS [9,13].…”

“…Recently, we have demonstrated that basal calcium sensitization [determined in animals subjected to a blockade of major pressor systems -sympathetic nervous system (SNS) and renin-angiotensin system (RAS)] is decreased in adult SHR compared with Wistar-Kyoto (WKY) controls [13]. On the contrary, blood pressure (BP) response to the acute Rho kinase inhibition by fasudil or Y-27632 was found to be enhanced in SHR with intact SNS and RAS [9,13]. Unfortunately, the information about ontogenetic changes of calcium sensitization in normotensive and hypertensive animals is still missing.…”

The blocking of angiotensin II type 1 receptor and RhoA/Rho kinase activity in hypertensive patients: Effect of olmesartan medoxomil and implication with cardiovascular-renal remodeling

“…This could be the case, shown in animals, of low renin/hypervolemic hypertension, in which ROCK activity is increased despite low levels of Ang II, and the case of the reduction of ROCK activity in hypertensive patients on the calcium channel blocker amlodipine treatment, 30 although in this latter case a possible inhibitory effect on calcium entry in the cell, via an L-type voltage-dependent calcium channel, available for calcium sensitization by ROCK, might play a role. 33 In conclusion, this study demonstrates in hypertensive patients olmesartan's inhibitory effect on the RhoA/Rho kinase pathway likely via the reduction of oxidative stress signaling. This effect joined with the available evidence coming from the results of clinical trials in humans, further provides a mechanistic rationale for olmesartan's antioxidant and anti-inflammatory potential translation, in the long term, toward anti-atherosclerotic and anti-remodeling effects.…”