Nitric oxide blood pressure regulation

Nitric oxide is a regulator of vascular smooth muscle blockage of its formation from arginine causes an acute elevation of blood pressure, indicating that regulation of blood pressure is one of its many functions. 

Rees, D., Palmer, R. M. J., and Moncada, S. Role of endothelium-derived nitric oxide in the regulation of blood pressure. Proc. Natl. Acad. Set. U.S.A. 86, 3375-3378. 

Nitric oxide, synthesized in the body from the amino add arginine, serves as a chemical messenger in a variety of biological processes, including blood pressure regulation and the immune response. Its role in relaxation of smooth muscle in vascular tissues is shown in Fig. 10.4. 

Prizewinners Robal Furchgott and Louis Ignarro, independently, unraveled the role of nitric oxide in blood-pressure regulation. Cells in the lining of arteries detect increased blood pressure and respond by producing nitric oxide. NO rapidly diffuses through the artery wall to cells in the surrounding muscle tissue. In response, the muscle tissue relaxes, the blood vessel expands, and the blood pressure drops. 

Umans J, Levi R (1995) Nitric oxide in the regulation of blood flow and arterial pressure. Ann Rev Physiol 57 771-790... 

First described in the 1980s as "endothelium-derived relaxing factor," nitric oxide (NO) is a vasodilator believed to play a role in regulation of blood pressure under physiologic and pathophysiological conditions. For example, inhibition of NO synthesis under normal conditions and during septic shock results in a significant elevation of blood pressure. 

Figure 22.16 Regulation of vasoconstriction/vasodilation by angiotensin-II and bradykinin. The mechanism by which angiotensin-II stimulates vasoconstriction is shown in Figure 22.15. Angiotensin-converting enzyme is also responsible for bradykinin inactivation. Bradykinin stimulates endothelial cells to produce and secrete nitric oxide and prostacyclin, both of which are vasodilators. Consequently the effect of an ACE inhibitor is to decrease the concentration of angiotensin-II, which lowers blood pressure, and to increase the concentration of bradykinin, which also lowers blood pressure.

Physiologically, in both normal and hypertensive individuals, blood pressure is maintained by moment-to-moment regulation of cardiac output and peripheral vascular resistance, exerted at three anatomic sites (Figure 11-1) arterioles, postcapillary venules (capacitance vessels), and heart. A fourth anatomic control site, the kidney, contributes to maintenance of blood pressure by regulating the volume of intravascular fluid. Baroreflexes, mediated by autonomic nerves, act in combination with humoral mechanisms, including the renin-angiotensin-aldosterone system, to coordinate function at these four control sites and to maintain normal blood pressure. Finally, local release of vasoactive substances from vascular endothelium may also be involved in the regulation of vascular resistance. For example, endothelin-1 (see Chapter 17) constricts and nitric oxide (see Chapter 19) dilates blood vessels. 

Butoxy-benzonitrile derivatives prepared by Birkinshaw (4), (III), were effective as nitric oxide synthase inhibitors and used in the treatment of smooth muscle relaxation disorders and in the regulation of blood pressure and blood flow. 

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