Contribution Of T-Type Ca2+Channels To Blood Pressure Regulation In Genetically Hypertensive Rats.

L‐type Ca 2+ channels (LCC) play a major role in Ca 2+ influx into smooth muscle cells and cardiac myocytes. However, other Ca 2+ channels have been recognized to operate in the cardiovascular system of which the T‐type Ca 2+ channels (TCC) have been the focus of attention. Using a novel, highly selective TCC blocker we aimed to determine the contribution of TCC vs. LCC to blood pressure regulation in conscious SHR. Vehicle and equipotent doses of various calcium channels blockers were given IV for 24h. Mibefradil (0.25 mg/kg.h), Amlodipine (0.1 mg/kg.h), Verapamil (0.66 mg/kg.h), and Diltiazem (0.66 mg/kg.h) significantly lowered mean blood pressure (MBP) over 24h by −24±3, −20±4, −22±3, and −22±2 mmHg, respectively and caused tachycardia (5–15%), except Mibefradil. The TCC antagonist (T‐and L‐type IC 50 : 14 and 823 nM), given at 2.95 mg/kg.h IV lowered MBP transiently by −18 mmHg for 1–2h only without changing heart rate. Unbound plasma levels of the novel TCC blocker in vivo were almost 2 times the T‐type IC 50 and 0.03 times the L‐type IC 50 determined in vitro suggesting that the majority of TCC were blocked over 24h. Our studies suggest that the pharmacological effects of the calcium channel blockers tested, including Mibefradil, are due mostly to inhibition of L‐type Ca 2+ channels and that inhibition of T‐type Ca 2+ channels causes acute, transient decreases in blood pressure in conscious genetically hypertensive rats.