Cross-talking between calcium and histamine in the expression of MAPKs in hypertensive vascular smooth muscle cells

Abstract

Histamine (HA) is one of many neurotransmitters that have been implicated in cardiovascular functioning. Alterations in vascular smooth muscle due to the effects of histamine have been suggested. We investigated the modulatory effect of HA on mitogen activated protein kinase (MAPK) expression, specifically extracellular regulating kinase (ERK) 1 & 2 in vascular smooth muscle cells (VSMCs) from both spontaneously hypertensive (SHR) and control Wistar Kyoto (WKY) rats. Cross-talking between calcium (Ca2+) and HA during HA-induced modulatory effect on MAPK expression in SHR VSMCs was also investigated. A stimulatory increase in expression of ERK 1 & 2 was observed to be dose and time dependent with maximum expression occurring within 5 min in both SHR and WKY VSMCs. The stimulatory increase in expression is persistent for 60 min in SHR VSMCs, whereas, in WKY cells the stimulatory effect persists for only 20 min. Mepyramine, the H1 receptor antagonist, reduced the HA-induced increase in ERK 1 & 2 significantly in SHR VSMCs. A reduction in the HA stimulated increase in ERK 1 & 2 expression was observed at 20 min of exposing cells to diltiazem, the calcium channel blocker, whereas, the calcium chelator, BAPTA effect on ERK 1 & 2 expression was observed within 5 min in SHR VSMCs. The data demonstrates that cross-talking occurs between HA stimulation and Ca2+ induction during HA-induced activation of ERK 1 & 2 in VSMCs of both cell types. Although both intracellular calcium ([Ca2+]i) and extracellular Ca2+ maybe involved in the activation of ERK 1 & 2 by HA, the dependence on [Ca2+]i is more dramatic than the dependence on extracellular Ca2+ in hypertensive cells, which may contribute to the role of HA as a risk factor of hypertension in VSMCs of the aorta.