Changes in mechanical responses of vascular smooth muscles to acetylcholine, noradrenaline and high-potassium solution in hypercholesterolemic rabbits.

Mechanical responses produced by high potassium solution (high-[K]), noradrenaline (NA) and acetylcholine (ACh) were observed in the thoracic aorta and the main pulmonary artery isolated from control and hypercholesterolemic rabbits. In the hypercholesterolemic rabbit, these tissues showed increased contractile sensitivity to high-[K], in comparison with those from the control rabbit. In tissues from the control rabbit, mechanical removal of the endothelium did not change the contraction to high-[K]. The amplitudes of the contractions produced by NA were decreased in tissues from the hypercholesterolemic rabbit, while they were enhanced after removal of the endothelium in tissues from the control rabbit. The endothelium-dependent relaxant response to ACh observed in tissues from the control rabbit was diminished, abolished or changed to a contraction in tissues from the hypercholesterolemic rabbit. It is concluded that in vascular tissues from the rabbit, an increase in contractile sensitivity to high-[K], a decrease in sensitivity to NA and dysfunction of the endothelium to ACh are induced by feeding a high-cholesterol diet and these changes in the vascular tissues may thus be involved in the hypertension observed during diet-induced atherosclerogenesis.