Smooth muscle tonus

Major effector proteins for G-pro-tein-coupled receptors include adenylate cyclase (ATP intracellular messenger cAMP), phospholipase C (phos-phatidylinositol intracellular messengers inositol trisphosphate and di-acylglycerol), as well as ion channel proteins. Numerous cell functions are regulated by cellular cAMP concentration, because cAMP enhances activity of protein kinase A, which catalyzes the transfer of phosphate groups onto functional proteins. Elevation of cAMP levels inter alia leads to relaxation of smooth muscle tonus and enhanced contractility of cardiac muscle, as well as increased glycogenolysis and lipolysis (p. 

The diagnosis is suspected when decreased renal function is associated with dilatation of the collecting system on US (Fig. 3.8). However, such dilatation may be passive, due to two phenomena either a full bladder, requiring repeated US after complete voiding or bladder catheterization, or a loss of smooth-muscle tonus secondary to ureteral denervation. Unfortunately, this latter mechanism is difficult to confirm usually it occurs very early after transplantation and dilatation is observed during follow-up, despite persistently normal renal function. 

Smooth muscle effects. The opposing effects on smooth muscle (A) of a-and p-adrenoceptor activation are due to differences in signal transduction (p. 66). This is exemplified by vascular smooth muscle (A). ai-Receptor stimulation leads to intracellular release of Ca + via activation of the inositol tris-phosphate (IP3) pathway. In concert with the protein calmodulin, Ca + can activate myosin kinase, leading to a rise in tonus via phosphorylation of the contractile protein myosin. cAMP inhibits activation of myosin kinase. Via the former effector pathway, stimulation of a-receptors results in vasoconstriction via the latter, P2-receptors mediate vasodilation, particularly in skeletal muscle - an effect that has little therapeutic use. 

Mechanisms of action. The tonus of vascular smooth muscle can be decreased by various means. ACE inhibitors, antagonists at ATI-receptors and antagonists at a-adrenoceptors protect against the effects of excitatory mediators such as angiotensin 11 and norepinephrine, respectively. Prostacyclin an-Ltillmann, Color Atlas of Pharmacology 2000 Thieme All rights reserved. Usage subject to terms and conditions of license. 

Pharmacology Trospium is an antispasmodic, antimuscarinic agent. Trospium antagonizes the effect of acetylcholine on muscarinic receptors in cholinergically innervated organs. Its parasympatholytic action reduces the tonus of smooth muscle in the bladder. Trospium increases maximum cystometric bladder capacity and volume at first detrusor contraction. 

At the bronchi, predominantly /32-adrenoceptors are present on the smooth muscle cells. Therefor noradrenaline has hardly any influence on the muscular tonus whereas adrenaline induce a dilatation especially of precontracted bronchi, independent of the cause (histamine, acetylcholine, kinines, prostanoides). This effect can be used therapeutically in the therapy of bronchial asthma. In general the local application by aerosol is more useful than the systemic application, due to lesser side effects and the additional, beneficial effect of the reduction of mucosa swelling. 

The effect of catecholamines on the human uterus, which can be mediated by a- and /3-adrenoceptors, depends on its functional state. During pregnancy /32-adrenoceptor stimulation decrease the uteral tonus, an effect that can be used therapeutically. /32-Adrenoceptor agonists are in use as tocolytics. In the bladder base and the urethral sphincter a-adrenoceptors are present, mediating a contraction, whereas the /32-adrenoceptors of the bladder wall induce a relaxation of the particular smooth muscles present at these structures. Ejaculation is regulated by a-adrenoceptors. 

Mechanism of Action A urinary antispasmodic t hat act s as a direct antagonist at muscarinic acetylcholine receptors in cholinergically innervated organs. Reduces tonus (elastictension) of smooth muscle in the bladder and slows parasympathetic contractions. Therapeutic Effect Decreases urinary bladder contractions, increases residual urine volume, and decreases detrusor muscle pressure. 

In ordinary doses, meperidine exerts inappreciable effects on respiration and circulation. In large doses, it interferes with the facilitatory function of the pneumotaxic center and the vagal afferent impulses, thereby reducing the rate and depth of respiration. With still higher doses, meperidine produces an irregular respiratory rhythm and ultimately induces apnea. It causes relaxation of the ureter, gall bladder, and bronchi. This action is partly a direct one on the smooth muscle of these structures and, in part, a result of its anticholinergic activity. It does not affect the size of the pupil or alter the tonus of the uterus. 

Papaverine (6,7,3, 4 -tetramethoxy-l-benzylisoquinoline) was isolated for the first time by Merck (35) from opium. In 1914, Pal (36) demonstrated on animals in vivo that papaverine decreases the tonus of the smooth muscle without affecting its natural mobility. It is a... 

Mechanisms of action. The tonus of vascular smooth muscle can be decreased by various means. 

Direct action on vascular smooth muscle cells. Ca2+-channel blockers (p.126) and K1 channel openers (diazoxide, minoxidil) act at the level of channel proteins to inhibit membrane depolarization and excitation of vascular smooth muscle cells. Phosphodiesterase (PDE) inhibitors retard the degradation of intracellular cGMP, which lowers contractile tonus. Several PDE isozymes with different localization and function are known. 

The peripheral effects concern the motility and tonus of gastrointestinal smooth muscle segmentation is enhanced but propulsive peristalsis is inhibited. The tonus of sphincter muscles is markedly raised (spastic constipation). The antidiarrhetic effect is used therapeutically (loperamide, p.180). Gastric emptying is delayed (pyloric spasm) and drainage of bile and pancreatic juice is impeded because the sphincter of Oddi contracts. Likewise, bladder function is affected specifically bladder emptying is impaired owing to an increased tone of the vesicular sphincter. 

Because capillary walls are thin (to permit diffusion) the blood that is delivered to them must be delivered under reduced pressure. This is accomplished by the arterioles, which combine relatively muscular walls with a narrow lumen. The arterial blood pressure is a function of cardiac output and the total peripheral vascular resistance, which is primarily a function of the degree of normal tension (tonus) of the smooth muscle cells in the walls of the arterioles. If this tonus increases above the normal range for extended periods of time, hypertension (high blood pressure) will result. This tonus is under the control of the autonomic nervous system and of adrenergic hormones (catecholamines). 

Spastic contractions in smooth muscles in the gastrointestinal, biliary and urinary tracts and uterus may be caused by parasympathetic tonus, gallstones or kidneystones or ischaemia. It is of great practical clinical interest to be able to relieve these spasms, whatever their aetiology. 

An aromatized alkaloid of this derivation, papaverine (31) is the most important alkaloid of the BIQ group from the pharmacological point of view. Papaverine inhibits aldol reductase, GABA and glucose response in chemosensory cells, and phosphodiesterase (Wink, 1993). In vivo, this alkaloid decreases the tonus of the smooth muscle, increases coronary artery flow, and causes dilation. Papaverine has a beneficial effect on angina pectoris. This aromatic isoquinoline alkaloid is neither narcotic nor addictive (Cordell, 1981). Papaverine has an LD50 i.v. in mouse of 27.5 mg/kg. Demethylpa-paverine inhibits aldose reductase (Wink, 1993). 

In blood vessels, the relaxant action of ACh on muscle tone is indirect, because it involves stimulation of M3-cho-linoceptors on endothelial cells that respond by liberating NO (= endothelium-derived relaxing factor). The latter diffuses into the subjacent smooth musculature, where it causes a relaxation of active tonus (p. 121). 

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