821 AGE-RELATED DIFFERENCES IN BLOOD PRESSURE RESPONSE TO ACUTE BLOCKADE OF CALCIUM INFLUX AND CALCIUM SENSITIZATION IN WISTAR-KYOTO AND SPONTANEOUSLY HYPERTENSIVE RATS

Abstract

Background: Spontaneously hypertensive rats (SHR) are characterized by augmented Ca2+ influx through L-type voltage-dependent calcium channels (L-VDCC), which is one of the most important factors responsible for increased blood pressure (BP). The altered BP regulation in hypertension also includes RhoA/Rho-kinase pathway playing pivotal role in Ca2+ sensitization. The ontogenetic development of Ca2+ influx and Ca2+ sensitization has not been fully examined. Our study was aimed to determine the contribution of these two mechanisms to BP maintenance in conscious normotensive Wistar-Kyoto rats (WKY) and SHR at different ages. Design and methods: BP response to acute intravenous administration of cumulative doses of L-VDCC blocker (nifedipine) or Rho kinase inhibitor (fasudil) was determined in 3-, 5-, 7-, 13-, and 26-week-old WKY and SHR. Results: There were no significant differences in BP response to nifedipine induced L-VDCC blockade in all age groups of WKY rats, while in SHR BP response increased with age and/or hypertension level. The same was true for Rho kinase inhibition. In 3-week-old rats nifedipine-sensitive BP components were identical in both strains, whereas BP response to fasudil was greater in 3-week-old WKY than in prehypertensive SHR. Finally, the fasudil-sensitive BP component was greater in 13- and 26-week-old SHR than WKY. Conclusions: Ca2+ influx through L-VDCC and Ca2+ sensitization mediated by RhoA/Rho-kinase pathway are involved in the regulation of vascular tone in both strains. Both mechanisms are augmented in rats with developed hypertension, but RhoA/Rho-kinase pathway seems to be diminished in prehypertensive SHR. Partially supported by grant 304/12/0259 (GA CR).