OS 05-03 DECREASED RHO-KINASE-BASED CALCIUM SENSITIZATION IN HYPERTENSIVE REN-2 TRANSGENIC RATS (TGR)

Abstract

Objective: Comparing BP response to Ca channel opener BAY K8644 prior and after Rho kinase inhibition we demonstrated lowered calcium sensitization in spontaneously hypertensive rats (SHR), although BP response of intact SHR to Rho kinase inhibitor fasudil was enhanced (Behuliak et al. J Hypertens 31:2025,2013). The aim of the present study was to evaluate calcium sensitization in hypertensive TGR and their normotensive HanSD controls using the same methods. We also tried to elucidate the interference of baroreflex-activated sympathetic activity with BP response to fasudil. Design and Method: Blood pressure and heart rate responses to increasing doses of BAY K8644 (opener of L type voltage-dependent calcium channels) was determined in conscious heterozygous TGR rats (subjected to acute RAS and SNS blockade). BP response was recorded prior and after Rho kinase inhibition by fasudil and calcium sensitization was estimated from the difference between both BP response curves. Furthermore, BP-lowering effects of acute administration of increasing fasudil doses were measured in conscious intact rats and in rats subjected to combined blockade of RAS, SNS and NOS in which baroreflex efficiency was suppressed. Results: Using the BAY K8644-based approach we demonstrated moderately attenuated calcium sensitization in hypertensive TGR but enhanced acute BP response to fasudil in intact TGR compared to HanSD rats. This was accompanied by greater heart rate increase in HanSD than in TGR, indicating attenuated baroreflex efficiency in hypertensive TGR. If baroreflex operation was minimized by ganglionic blockade, fasudil-induced BP fall was substantially augmented in HanSD but unchanged in TGR. Conclusions: Calcium sensitization is attenuated in hypertensive TGR, this change being evident only in the absence of sympathetic nervous system which compensates BP changes elicited by acute Rho kinase inhibition better in normotensive than in hypertensive animals. Supported by grant AZV 15–25396A (MH CR)