Differential alteration of vascular reactivity in rabbit aorta with modest elevation of serum cholesterol

The effect of diet-induced, moderate elevation of serum cholesterol on vascular reactivity in isolated rabbit abdominal aortic rings was examined by using a series of vasoconstrictor and vasodilator agonists. Serum cholesterol of rabbits that were fed a cholesterol-free, casein-rich diet for 10 weeks was elevated approximately 4.5-fold compared with values found in control rabbits that were fed standard lab chow (223 +/- 41 versus 51 +/- 5 mg/dl, respectively). Relaxation responses to carbamylcholine chloride and (+/-)-isoproterenol hydrochloride in vessels from hypercholesterolemic rabbits were markedly inhibited in the presence of norepinephrine, prostaglandin F2 alpha, 5-hydroxytryptamine, and angiotensin II but not in the presence of phorbol 12,13-dibutyrate. The depressed vasodilation in hypercholesterolemic vessels appeared to depend on the agonist initiating the contraction. Sodium nitroprusside-induced relaxations were unchanged in rings from hypercholesterolemic rabbits compared with rings from control rabbits for all contractile agonists except KCl. Isolated aortic rings from hypercholesterolemic rabbits exhibited a slight but significantly increased vasoconstrictor sensitivity to 5-hydroxytryptamine and KCl but not to norepinephrine, prostaglandin F2 alpha, angiotensin II, or phorbol 12,13-dibutyrate compared with aortic rings from control rabbits. These results demonstrate that modest elevation of serum cholesterol is sufficient to depress vasodilator and enhance vasoconstrictor responses to certain agonists. Vasodilator effects are impaired to a greater extent by a small increase in serum cholesterol than are responses to vasoconstrictor agonists. It is postulated that the induction of differential alterations in vascular reactivity with moderate increase in serum cholesterol may represent important early events predisposing arteries to vasospasm.