[PP.31.05] ALTERED CALCIUM SENSITIZATION IN HYPERTENSIVE REN-2 TRANSGENIC RATS

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Abstract

Objective:

A comparison of BP response to Ca channel opener BAY K8644 prior and after Rho kinase inhibition indicated decreased calcium sensitization in spontaneously hypertensive rats (SHR), although blood pressure (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 transgenic rats with murine Ren-2 gene (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 BAY K8644 (opener of L type voltage-dependent calcium channels) was determined in conscious 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 as well as in rats subjected to combined blockade of RAS, SNS and NOS in which baroreflex efficiency was suppressed.

Results:

Using the above BAY K8644-based approach we demonstrated moderate attenuation of calcium sensitization in hypertensive TGR. We also observed enhanced acute BP response to fasudil in intact TGR compared to HanSD rats. This different BP response was accompanied by more pronounced heart rate increase in HanSD than in TGR, indicating attenuated baroreflex efficiency in hypertensive TGR. If baroreflex operation was minimized by ganglionic blockade in rats subjected to combined RAS, SNS and NO synthase blockade, fasudil-induced BP fall was manifold augmented in HanSD but unchanged in TGR, suggesting the importance of baroreflex-activated sympathetic activity in compensation of fasudil-induced BP changes.

Conclusions:

Calcium sensitization is attenuated in hypertensive TGR compared to normotensive controls, but this difference can be seen only in the absence of operating sympathetic nervous system which compensates BP changes elicited by acute Rho kinase inhibition much better in normotensive than in hypertensive animals.

Conclusions:

Partially supported by grant AZV 15–25396A (MH CR)

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