Vascular smooth-muscle tone

Sturm, R.J., Holloway, D.A., Buckley, S., Osborne, M.C., Grimes, D., Wcichmann, B.M. and Rimele, T.J. (1989). Potential regulatory role of inflammatory cells on local vascular smooth muscle tone. Agents Actions, 27, 414—417. 

Blood pressure and electrolyte composition by regulating mechanisms involved with urine output, thirst, salt appetite, maintenance of plasma osmolarity, and vascular smooth muscle tone... 

Hypertension, or a chronic elevation in blood pressure, is a major risk factor for coronary artery disease congestive heart failure stroke kidney failure and retinopathy. An important cause of hypertension is excessive vascular smooth muscle tone or vasoconstriction. Prazosin, an aradrenergic receptor antagonist, is very effective in management of hypertension. Because oq-receptor stimulation causes vasoconstriction, drugs that block these receptors result in vasodilation and a decrease in blood pressure. 

Total peripheral resistance (TPR) is the resistance to blood flow offered by all systemic vessels taken together, especially by the arterioles, which are the primary resistance vessels. Therefore, MAP is regulated by cardiac activity and vascular smooth muscle tone. Any change in CO or TPR causes a change in MAP. The major factors that affect CO, TPR, and therefore MAP, are summarized in Figure 15.3, as well as in Table 15.1. These factors may be organized into several categories and will be discussed as such ... 

Substances released from many cells and tissues in the body, including the endothelium lining blood vessels, endocrine glands, and myocytes in the heart, may affect vascular smooth muscle tone. These substances may stimulate this muscle to cause vasoconstriction or inhibit it to cause vasodilation. As expected, vasoconstriction will increase TPR (and therefore MAP) and vasodilation will decrease TPR (and therefore MAP). 

The major circulating hormones that influence vascular smooth muscle tone are the catecholamines epinephrine and norepinephrine. These hormones are released from the adrenal medulla in response to sympathetic nervous stimulation. In humans, 80% of catecholamine secretion is epinephrine and 20% is norepinephrine. Stimulation of cy-adrenergic receptors causes vasoconstriction. The selective a,-adrenergic receptor antagonist, prazosin, is effective in management of hypertension because it causes arterial and venous smooth muscle to relax. 

The vascular endothelium produces a number of substances that are released basally into the blood vessel wall to alter vascular smooth muscle tone. One such substance is endothelin (ET-1). Endothelin exerts its effects throughout the body, causing vasoconstriction as well as positive inotropic and chronotropic effects on the heart. The resulting increases in TPR and CO contribute to an increase in MAP. Synthesis of endothelin appears to be enhanced by many stimuli, including Ag II, vasopressin, and the mechanical stress of blood flow on the endothelium. Synthesis is inhibited by vasodilator substances such as prostacyclin, nitric oxide, and atrial natriuretic peptide. There is evidence that endothelin is involved with the pathophysiology of many cardiovascular diseases, including hypertension, heart failure, and myocardial infarction. Endothelin receptor antagonists are currently available for research use only. 

Bronchiolar smooth muscle is sensitive to changes in carbon dioxide levels. Excess carbon dioxide causes bronchodilation and reduced carbon dioxide causes bronchoconstriction. Pulmonary vascular smooth muscle is sensitive to changes in oxygen levels excess oxygen causes vasodilation and insufficient oxygen (hypoxia) causes vasoconstriction. The changes in bronchiolar and vascular smooth muscle tone alter the amount of ventilation and perfusion in a lung unit to return the V/Q ratio to one. 

Kurebayashi N, Ogawa Y 2001 Depletion of Ca2+ in the sarcoplasmic reticulum stimulates Ca2+ entry into mouse skeletal fibres. J Physiol 533 185-199 Laporte R, Laher I 1997 Sarcoplasmic reticulum-sarcolemma interactions and vascular smooth muscle tone. J Vase Res 34 325—343... 

NO has a significant effect on vascular smooth muscle tone and blood pressure. Numerous endothelium-dependent vasodilators, such as acetylcholine and bradykinin, act by increasing intracellular calcium levels, which induces NO synthesis (Figure 19-2). Mice with a knockout mutation in the eNOS gene display increased vascular tone and elevated mean arterial pressure, indicating that eNOS is a fundamental regulator of blood pressure. The effects of vasopressor drugs are increased by inhibition of NOS. 

Adenosine affects vascular smooth muscle tone in the pulmonary circulation. In the feline pulmonary vascular bed, under conditions of controlled pulmonary blood flow and constant left atrial pressure, adenosine was shown to produce dose-dependent, tone-dependent responses (Neely and Matot 1996 Cheng et al. 1996). At low baseline pulmonary vascular tone adenosine induces vasoconstriction via A3AR and the release of prostanoids, whereas at elevated pulmonary vascular tone it produces vasodilatation by acting on A2AR, without nitric oxide release or the activation of guanylate cyclase or KATp channels (Neely and Matot 1996 Cheng et al. 1996). 

Vascular smooth muscle tone is regulated by adrenoceptors consequently, catecholamines are important in controlling peripheral vascular resistance and venous capacitance. Alpha receptors increase arterial resistance, whereas 2 receptors promote smooth muscle relaxation. There are major differences in receptor types in the various vascular beds (Table 9-4). The skin vessels have predominantly receptors and constrict in the presence of epinephrine and norepinephrine, as do the splanchnic vessels. Vessels in skeletal muscle may constrict or dilate depending on whether ffor 13 receptors are activated. Consequently, the overall effects of a sympathomimetic drug on blood vessels depend on the relative activities of that drug at and 8receptors and the anatomic sites of the vessels affected. In addition, Di receptors promote vasodilation of renal, splanchnic, coronary, cerebral, and perhaps other resistance vessels. Activation of the Di receptors in the renal vasculature may play a major role in the natriuresis induced by pharmacologic administration of dopamine. 

Another important property of dopamine is its ability to inhibit sympathetic nerve function by interacting with presynaptic dopaminergic receptors to decrease norepinephrine release (10). These receptors are not adenylate cyclase coupled and have been classified as D-2 (8). Activation of cardiac presynaptic dopamine receptors causes bradycardia, and of vascular presynaptic dopamine receptors passive vasodilation, the magnitude of which will depend on the contribution of adrenergic activity to maintaining heart rate and vascular smooth muscle tone (11,12). 

Hypertension is defined as a sustained diastolic blood pressure greater than 90 mm Hg accompanied by an elevated systolic blood pressure (>140 mm Hg). Hypertension results from increased peripheral vascular smooth muscle tone, which leads to increased arteriolar resistance and reduced capacitance of the venous system. Elevated blood pressure is an extremely common disorder, affecting approximately 15% of the population of the United States (60 million people). Although many of these individuals have no symptoms, chronic hypertension—either systolic or diastolic—can lead to congestive heart failure, myocardial infarction, renal damage, and cerebrovascular accidents. The incidence of morbidity and mortality significantly decreases when hypertension is diagnosed early and is properly treated. 

Vascular smooth muscle tone Reduction of blood pressure... 

Reduction of blood pressure and tissue perfusion by relaxing vascular smooth muscle tone... 

Nifedipine ( Adalat, Bayer 10A0)(20), used for the treatment of angina, 87 is a powerful peripheral vasodilator and has hypotensive properties in man.88 A dose of 30mg sublingually lowered blood pressure substantially in 1A essential hypertensives for more than k hrs. with a rise in heart rate and plasma renin activity. Nifedipine interferes with the transmembrane calcium flux causing a reduction in vascular smooth muscle tone.87)89 The conformational requirement for dopamine induced renal... 

The ion-channel accessory subunits are also the targets of various compounds, indicating their importance to the pharmaceutical industry. The smooth muscle-specific (3-1 subunit of the Kcal-1 (BK.) channel has profound effects in regulating vascular smooth muscle tone, and thus blood pressure, as well as urinary bladder (where it is most heavily expressed) contractility. Targeting the Kcal-1 channel (3-1 subunit may lead to novel therapeutics to control blood pressure and urinary incontinence. The Kcal-1 channel has a... 

Walsh, M.P., Kargacin, G.J., Kendrick-Jones, J., and Lincoln, T.M. (1995) Intracellular mechanisms involved in the regulation of vascular smooth muscle tone. Canadian Journal of Physiology 8t Pharmacology, 73 565-573. 

Lincoln TM, Koraalavilas P, Cornwell TL (1994) Pleiotropic regulation of vascular smooth muscle tone by cyclic GMP-dependent protein kinase. H rtension... 

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