Impaired Ca2+ handling in penile arteries from prediabetic Zucker rats: involvement of Rho kinase

Villalba N, Contreras C, Hernandez M, Garcia-Sacristan A, Prieto D. Impaired Ca2+ handling in penile arteries from prediabetic Zucker rats: involvement of Rho kinase. Am J Physiol Heart Circ Physiol 300: H2044-H2053, 2011. First published February 4, 2011; doi: 10.1152/ajpheart.01204.2010.-Diabetes is associated with an increased vascular tone usually involved in the pathogenesis of diabetic cardiovascular complications such as hypertension, stroke, coronary artery disease, or erectile dysfunction (ED). Enhanced contractility of penile erectile tissue has been associated with augmented activity of the RhoA/Rho kinase (RhoK) pathway in models of diabetes-associated ED. The present study assessed whether abnormal vasoconstriction in penile arteries from prediabetic obese Zucker rats (OZRs) is due to changes in the intracellular Ca2+ concentration ([Ca2+](i)) and/or in myofilament Ca2+ sensitivity. Penile arteries from OZRs and lean Zucker rats (LZRs) were mounted on microvascular myographs for simultaneous measurements of [Ca2+](i) and tension. The relationships between [Ca2+] i and contraction for the alpha(1)-adrenergic vasoconstrictor phenylephrine (PE) were left shifted and steeper in OZRs compared with LZRs, although the magnitude of the contraction was similar in both groups. In contrast, the vasoconstriction induced by the thromboxane A(2) receptor agonist U-46619 was augmented in arteries from OZRs, and this increase was associated with an increase in both the sensitivity and maximum responses to Ca2+. The RhoK inhibitor Y-27632 (10 mu M) reduced the vasoconstriction induced by PE to a greater extent in OZRs than in LZRs, without altering Ca2+. Y-27632 inhibited with a greater potency the contraction elicited by high KCl in arteries from OZRs compared with LZRs without changing [Ca2+](i). RhoK-II expression was augmented in arteries from OZRs. These results suggest receptor-specific changes in the Ca2+ handling of penile arteries under conditions of metabolic syndrome. Whereas augmented vasoconstriction upon activation of the thromboxane A(2) receptor is coupled to enhanced Ca2+ entry, a RhoK-mediated enhancement of myofilament Ca2+ sensitivity is coupled with the alpha(1)-adrenergic vasoconstriction in penile arteries from OZRs.