The role of nitric oxide synthase/nitric oxide in vascular smooth muscle control

Vascular compliance is dependent on endogenous and exogenous sources of nitric oxide (NO). In a discussion of therapeutics and NO derived via nitric oxide synthase (NOS) enzymes, it is necessary to examine the pathways of each drug to provide the clinical perfusionist with a greater understanding of the role of NOS/NO in vascular function. Endothelial-derived NO is a contributor in the vasoregulation of vascular smooth muscle. Therapeutics seek to mimic the vasodilatory effects of the endogenous NO. The therapeutics included in this review are nitroglycerin, nitroprusside, amyl nitrite, and inhalation of NO. L-Arginine supplementation provides additional substrate for the endogenous pathway that can augment NO production. NO is a small bioactive molecule involved in various biochemical pathways. Dysregulation of NO production can impair normal physiologic control of vascular compliance. Therefore, the purpose of this review is to provide the perfusionist with an understanding of the biochemical and pharmacological aspects of NOS/NO associated with vascular function.

Download Full-text

Role of Aging Versus the Loss of Estrogens in the Reduction in Vascular Function in Female Rats

Endocrinology ◽

10.1210/en.2008-0640 ◽

2008 ◽

Vol 150 (1) ◽

pp. 212-219 ◽

Cited By ~ 27

Author(s):

James P. Stice ◽

Jason P. Eiserich ◽

A. A. Knowlton

Keyword(s):

Nitric Oxide ◽

Smooth Muscle ◽

Nitric Oxide Synthase ◽

Vascular Smooth Muscle ◽

Guanylyl Cyclase ◽

Vascular Function ◽

Soluble Guanylyl Cyclase ◽

Female Rats ◽

Oxide Synthase

Although aging is known to lead to increased vascular stiffness, the role of estrogens in the prevention of age-related changes in the vasculature remains to be elucidated. To address this, we measured vascular function in the thoracic aorta in adult and old ovariectomized (ovx) rats with and without immediate 17β-estradiol (E2) replacement. In addition, aortic mRNA and protein were analyzed for proteins known to be involved in vasorelaxation. Aging in combination with the loss of estrogens led to decreased vasorelaxation in response to acetylcholine and sodium nitroprusside, indicating either smooth muscle dysfunction and/or increased fibrosis. Loss of estrogens led to increased vascular tension in response to phenylephrine, which could be partially restored by E2 replacement. Levels of endothelial nitric oxide synthase and inducible nitric oxide synthase did not differ among the groups, nor did total nitrite plus nitrate levels. Old ovx exhibited decreased expression of both the α and β-subunits of soluble guanylyl cyclase (sGC) and had impaired nitric oxide signaling in the vascular smooth muscle. Immediate E2 replacement in the aged ovx prevented both the impairment in vasorelaxation, and the decreased sGC receptor expression and abnormal sGC signaling within the vascular smooth muscle. The combination of loss of estradiol and aging leads to increased constriction (phenylephrine) and decreased relaxation with nitric oxide. Reduced soluble guanylyl cyclase mediates these changes.

Download Full-text

TNF-alpha and IFN-gamma induce expression of nitric oxide synthase in cultured rat medullary interstitial cells

AJP Renal Physiology ◽

10.1152/ajprenal.1995.269.2.f212 ◽

1995 ◽

Vol 269 (2) ◽

pp. F212-F217 ◽

Cited By ~ 3

Author(s):

K. S. Lau ◽

O. Nakashima ◽

G. R. Aalund ◽

L. Hogarth ◽

K. Ujiie ◽

...

Keyword(s):

Nitric Oxide ◽

Smooth Muscle ◽

Nitric Oxide Synthase ◽

Vascular Smooth Muscle ◽

Guanylyl Cyclase ◽

Soluble Guanylyl Cyclase ◽

Tnf Alpha ◽

No Production ◽

Ifn Gamma ◽

Oxide Synthase

Cytokines increase the expression of the inducible (type II) nitric oxide synthase (NOS) in macrophages, liver, and renal epithelial cells. Previously, we found that cultured rat medullary interstitial cells (RMIC) contain high levels of soluble guanylyl cyclase. To determine whether these cells can also produce NO, we studied the effects of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) on NO production, NOS II mRNA, and NOS II protein expression. Both TNF-alpha and IFN-gamma, in the presence of a low concentration of the other cytokine, caused dose-dependent increases in NO production. Exposure to TNF-alpha and IFN-gamma stimulated the production of NOS II mRNA, as determined by Northern blotting. Restriction mapping of reverse transcription-polymerase chain reaction products indicated that normal cells contained macrophage NOS II, whereas cytokine-stimulated cells contained primarily vascular smooth muscle NOS II and some macrophage NOS II. The appearance of NOS II protein was demonstrated by Western blotting. RMIC cell guanosine 3',5'-cyclic monophosphate accumulation increased 129-fold in response to the cytokines. NOS inhibitors decreased nitrite production. We conclude that 1) TNF-alpha and IFN-gamma induce the expression of vascular smooth muscle NOS II and production of NO in RMIC, and 2) NO acts as an autocrine activator of the soluble guanylyl cyclase in RMIC.

Download Full-text