The relaxant response to carperitide

The relaxant response to carperitide was influenced neither by the removal of the endothelium nor by treatment with the nitric oxide synthase inhibitor or nitric oxide scavenger. This result was to be expected as previous studies showing that the vasodilator action of atrial natriuretic peptide is endothelium-independent and associated with increased cellular levels of cGMP as a result of activation of a particulate rather than a soluble guanylate cyclase in smooth muscle STF 083010 13, 14. Endothelium-independent action of carperitide is advantageous in operation theaters as the endothelium of bypass grafts are easily and frequently injured during harvest and anastomoses in coronary artery bypass surgery [15]. The relaxation induced by carperitide in the segments precontracted with 30 mM KCl was significantly less potent than with other vasoconstrictors even though nearly the same levels of cGMP were produced by carperitide in segments precontracted with 30 mM KCl and prostaglandin F2α. These results indicate that hyperpolarization through potassium channels mediates carperitide-induced relaxation. Increased cellular levels of cGMP have been shown to activate cGMP-dependent protein kinase, which promotes opening of calcium-sensitive potassium channels and efflux of potassium [16]. That leads to membrane hyperpolarization, inhibition of the voltage-gated calcium channel, and relaxation. High extracellular potassium concentration is thought to inhibit potassium efflux through cGMP-dependent protein kinase–activated calcium-sensitive potassium channels. The potential advantage of carperitide over other antispasm drugs such as nitroglycerin and nifedipine is that the pleiotropic effect can be expected, including cardioprotective 17, 18 and renoprotective effects 5, 19, as well as preventing left ventricular remodeling, arrhythmias [20], and ischemia-reperfusion injury. Higher cost is one of the weak points of carperitide compared with other vasodilators. Carperitide can be used topically and intravenously. Although perioperative infusion of carperitide can promise a certain level of favorable effects, one of the weaknesses of systemic administration is considered to be low blood pressure.