Nifedipine does not inhibit Bay K 8644-mediated vasoconstriction in vivo

Voltage-sensitive (VS) Ca²⁺ channel activity is dependent upon the redox state of the thiol-conlaining amino acids within the channels, making them susceptible to attack by reactive oxygen species during systemic inflammation. The aims of the present study were to characterize the in vivo vascular responses to the systemic administration of Bay K 8644, a specific L-type VS Ca²⁺ channel agonist, for studying the effects of systemic inflammation on VS Ca²⁺ channel function. The intravenous administration of Bay K 8644 (25-250 nmol/kg) produced dose-dependent increases in mean arterial blood pressure and mesenteric vascular resistance, while resistance in the hindquarter vasculature remained relatively unchanged. Surprisingly, these responses were not attenuated following the intravenous administration of nifedipine (500 nmol/kg), an L-type VS Ca²⁺ channel antagonist. To determine whether the dose of nifedipine was adequate to inhibit VS Ca²⁺ channel activity, the responses to norepinephrine were investigated prior to and following the administration of nifedipine. Norepinephrine (1-5 μg/kg) produced dose-dependent increases in mean arterial pressure and mesenteric vascular resistance, while resistance in the hindquarter vasculature remained relatively unchanged. The peak responses to norepinephrine were unchanged following the administration of nifedipine. suggesting that the recruitment of intracellular stores of calcium remained unaltered, however, the total area under the curve was significantly diminished, demonstrating significant inhibition of .VS Ca²⁺ channel opening in response to α-adrenooeptor stimulation. These studies demonstrate that Bay K 8644 produces a dose-dependent increase in blood pressure and vascular tone which is not mediated through the activation of L-type VS Ca²⁺ channels in vivo.