aortic pressure to eject blood;arterial blood pressure thus determines the systolic wall stress in an important way.Venous tone determines the capacity of the venous circulation and controls the amount of blood sequestered in the venous system versus the amount returned to the heart.Venous tone thereby determines the diastolic wall stress. The regulation of smooth muscle contraction and relaxation is shown schematically in Figure 1.As shown in Figures 1 and 2,drugs may relax vascular smooth muscle in several ways: (1)Increasing cGMP:As indicated in Figure 2,cGMP facilitates the dephosphorylation of myosin light chains,preventing the interaction of myosin with actin.Nitric oxide is an effective activator of soluble guanylyl cyclase and acts mainly through this mechanism.Important molecular donors of nitric oxide include nitroprusside and the organic nitrates used in angina. (2)Decreasing intracellular Ca:Calcium channel blockers predictably cause vasodilation because they reduce intracellular Ca2,a major modulator of the activation of myosin light chain kinase.(Beta blockers and calcium channel blockers reduce Ca2 influx in cardiac muscle,thereby reducing rate,contractility,and oxygen requirement unless reversed by compensatory responses.) (3)Stabilizing or preventing depolarization of the vascular smooth muscle cell membrane:The membrane potential of excitable cells is stabilized near the resting potential by increasing potassium permeability.Potassium channel openers,such as minoxidil sulfate,increase the permeability of K channels,probably ATP-dependent K*channels.Certain newer agents under investigation for use in angina (eg, nicorandil)may act,in part,by this mechanism. (4)Increasing cAMP in vascular smooth muscle cells:As shown in Figure 1,an increase in cAMP increases the rate of inactivation of myosin light chain kinase,the enzyme responsible for triggering the interaction of actin with myosin in these cells. This appears to be the mechanism of vasodilation caused by 2 agonists,drugs that are not used in angina. 33 aortic pressure to eject blood; arterial blood pressure thus determines the systolic wall stress in an important way. Venous tone determines the capacity of the venous circulation and controls the amount of blood sequestered in the venous system versus the amount returned to the heart. Venous tone thereby determines the diastolic wall stress. The regulation of smooth muscle contraction and relaxation is shown schematically in Figure 1. As shown in Figures 1 and 2, drugs may relax vascular smooth muscle in several ways: (1) Increasing cGMP: As indicated in Figure 2, cGMP facilitates the dephosphorylation of myosin light chains, preventing the interaction of myosin with actin. Nitric oxide is an effective activator of soluble guanylyl cyclase and acts mainly through this mechanism. Important molecular donors of nitric oxide include nitroprusside and the organic nitrates used in angina. (2) Decreasing intracellular Ca2+: Calcium channel blockers predictably cause vasodilation because they reduce intracellular Ca2+, a major modulator of the activation of myosin light chain kinase. (Beta blockers and calcium channel blockers reduce Ca2+ influx in cardiac muscle, thereby reducing rate, contractility, and oxygen requirement unless reversed by compensatory responses.) (3) Stabilizing or preventing depolarization of the vascular smooth muscle cell membrane: The membrane potential of excitable cells is stabilized near the resting potential by increasing potassium permeability. Potassium channel openers, such as minoxidil sulfate, increase the permeability of K+ channels, probably ATP-dependent K+ channels. Certain newer agents under investigation for use in angina (eg, nicorandil) may act, in part, by this mechanism. (4) Increasing cAMP in vascular smooth muscle cells: As shown in Figure 1, an increase in cAMP increases the rate of inactivation of myosin light chain kinase, the enzyme responsible for triggering the interaction of actin with myosin in these cells. This appears to be the mechanism of vasodilation caused by 2 agonists, drugs that are not used in angina