Clinical & Experimental Cardiology
Open Access
ISSN: 2155-9880
+44 1300 500008
ISSN: 2155-9880
+44 1300 500008
Naranjan S Dhalla
University of Manitoba, Canada
Keynote: J Clin Exp Cardiolog
Hypertension has been shown to be associated with an elevated level of intracellular Ca2+, which is determined by the functional status of both L-type Ca2+ channels and store-operated Ca2+ channels in the vascular smooth muscle. Although L-type Ca2+ antagonists such as verapamil are known to exert anti-hypertensive actions, the effects of store-operated blockers such as SKF-36365 (SK) on blood pressure and cell proliferation have not been examined. In this study, SK was observed to reduce systolic and diastolic blood pressures in rats in a dose and time dependent manner. While SK showed no effect on basal [Ca2+]i in rat aortic smooth muscle cells, the increase in [Ca2+]i due to lysophosphatidic acid (LPA) or angiotensin II was depressed by this agent. On the other hand, norepinephrine- or the endothelin-induced increase in [Ca2+]i was not affected by SK. The cell proliferation, as determined by cell number as well as thymidine incorporation in the absence or presence of LPA, was reduced by SK. This agent was also observed to augment the verapamil-induced reduction in diastolic blood pressure without any effect on the verapamil-induced reduction in systolic blood pressure. In addition, verapamil was found to depress LPA-induced or ATP-induced increase in [Ca2+]i, these actions of verapamil were promoted by SK. The results suggest that store-operated Ca2+ channel blockers, which affect sites different from those for L-type Ca2+ channel antagonists, either alone or in combination, may be useful for the treatment of hypertension.
Naranjan S Dhalla is a distinguished Professor at the University of Manitoba and is the Director of Cardiovascular Developments at the St. Boniface Hospital Albrechtsen Research Centre. He has been investigating the pathophysiology and pharmacology of heart disease and has published 794 full length papers. His research work has been cited more than 22,600 times with h-factor of 71. He has given 350 symposia talks at various national and international conferences in addition to 340 talks at different institutions. He has received more than 178 honours and awards, including six honorary doctorate degrees and four honorary professorships from institutions all over the world.
Email: nsdhalla@sbrc.ca