Blood pressure, control with nitric oxide

We evaluated whether the Mn(ii)-based SOD mimics could potentiate the levels of nitric oxide, a potent vasorelaxant. Superoxide reacts with nitric oxide in a diffusion-controlled manner to produce peroxynitrite. By catalyzing the dismu-tation of superoxide, SOD mimics would be expected to increase nitric oxide levels. The SOD mimic SC-52608 enhanced nitric oxide levels (as assessed by cyclic GMP activity) in rat lung fibroblasts in a dose-dependent manner. SC-52608 induced the relaxation of preconstricted rat aortic rings. The aortic ring relaxation was endothelium-dependent and inhibitable by a nitric oxide synthase inhibitor. Intravenous administration of SC-52608 into conscious rats resulted in a transient, dose-dependent decrease in blood pressure. The results are consistent with the SOD mimic SC-52608 potentiating levels of nitric oxide, which causes the observed relaxation of the aortic rings and the decrease in 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. 

Vitamin C appears to be more promising. Theoretically, this vitamin functions as an antioxidant that would enhance the synthesis or prevent the breakdown of nitric oxide, a naturally occurring gas produced in the lining of the arteries that keeps those vessels flexible and more capable of vasodilation. Studies have shown reductions in systolic blood pressure though not in diastolic pressure, when subjects were treated with vitamin C. A randomized, placebo-controlled trial with thirty-nine patients yielded nice results. Subjects took a 2 gram loading dose and then 500 mg daily for thirty days. Systolic blood pressure was reduced by 13 mm Hg, but vitamin C had no effect on diastolic pressure. 

The aim of the second Israeli study with tomato extract was to evaluate the potential change in systolic and diastolic blood pressure in treated but uncontrolled hypertensive patients after an eight-week treatment period. Dr. Paran and her colleagues also studied changes in nitric oxide during treatment. This was the gold standard of medical research a randomized, double-blind, crossover, placebo-controlled study. 

The same cardiovascular control system regulates blood distribution and blood pressure by affecting the small arterioles of the peripheral blood vasculature. The entrance to each of these vessels is surrounded by a sphincter muscle (a ring of involuntary muscle that surrounds the arteriolar aperture) with sympathetic, and in some cases, parasympathetic, nerve fibers. The sphincter is usually contracted. When the signal comes for the muscle to relax, the neuron produces nitric oxide at the neuromuscular junction, and this gas relaxes the sphincter. When the sphincter muscle expands, it increases the area through which blood flows and decreases its resistance. With decreased resistance, blood pressure falls. 

Lentinan and ABPS stimulate the release of tumor necrosis factor (TNF)-a and nitric oxide (NO) from macrophages 9-10), NO is known as a bioregulatory agent in a wide variety of biological functions such as control of blood pressure, platelet aggregation, cytotoxicity of macrophages, and carcinogenesis 11-13), Thus, NO is likely to be associated with the antitumor activity of the mushroom polysaccharides. 

In the body, nitric oxide performs several critical biological functions as diverse as control of blood pressure, inhibition of platelet aggregation, cell differentiation, neurotransmission, and penile erection. It also plays a major role in the activity of the immune system. For example, macrophages (cells associated with the body s immune system) destroy bacteria and tumor cells by exposing them to nitric oxide. 

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