Blood pressure fall and increased relaxation of aortic smooth muscle in diabetic rats.

Abstract

This study was designed to identify changes in endothelium-independent relaxation that could contribute to the depressed vascular reactivity and fall in blood pressure (BP) detected in rats after 5 weeks of streptozotocin (STZ)-induced (i.e. type 1) diabetes. Aortic rings were contracted by simultaneous activation of voltage-operated channels (KCl=80 mM) and alpha-adrenergic receptors (phenylephrine 1 microM) and then relaxed by simultaneous exposure to Ca2+-free PSS and 10 microM phentolamine. Additional relaxations were performed under conditions in which the plasma membrane Na-Ca exchanger (PMNaCa) or Ca-pump (PMCA), or the sarcoplasmic reticulum (SR) Ca-pump (SERCA) were blocked, to identify which mechanism(s) could modulate this process. The STZ-diabetic rats had a moderate but significant decrease of BP, and their aortic rings exhibited accelerated relaxation following a biexponential model, with a significantly decreased slow component. In control rats only the inhibition of the PMNaCa could slow down the fast component, while the slow component was insensitive to any blocking maneuver. In contrast, the diabetic animals' slow component was sensitive to the inhibition of both the PMNaCa and the SERCA. The SERCA-sensitive 45Ca2+ uptake by the SR was augmented in the aortas of STZ-treated animals. This hyperactivity of the SERCA, associated with augmented activity of the PMNaCa, at least partly induced by an increase of the plasma membrane Na+/K+-ATPase activity, could explain the decrease in BP and the accelerated aortic relaxation observed in the diabetic rats.