Smooth muscle mechanisms

Pig. 2. Proposed mechanism of inbition of smooth muscle contraction by P2" gonists, where AMP is adenosine monophosphate, cAMP is cycHc-3 5 adenosine monophosphate, ATP is adenosine triphosphate, and -P is an attached phosphate. 

Soluble Compounds. The mechanism of barium toxicity is related to its ability to substitute for calcium in muscle contraction. Toxicity results from stimulation of smooth muscles of the gastrointestinal tract, the cardiac muscle, and the voluntary muscles, resulting in paralysis (47). Skeletal, arterial, intestinal, and bronchial muscle all seem to be affected by barium. 

The precise mechanism of nitrate action is not cleady understood and may be a combination of many factors. The basic pharmacologic action of nitrates is a relaxation of most vascular smooth muscle, eg, vascular, bronchial, gastrointestinal, uretal, uterine, etc. Vascular smooth muscle relaxation is a... 

Another mechanism in initiating the contraction is agonist-induced contraction. It results from the hydrolysis of membrane phosphatidylinositol and the formation of inositol triphosphate (IP3)- IP3 in turn triggers the release of intracellular calcium from the sarcoplasmic reticulum and the influx of more extracellular calcium. The third mechanism in triggering the smooth muscle contraction is the increase of calcium influx through the receptor-operated channels. The increased cytosolic calcium enhances the binding to the protein, calmodulin [73298-54-1]. 

When exposure is repeated, the allergen binds between two adjacent IgE molecules. This causes release of inflammatory mediators (histamine, leukotrienes, chemotactic factors). These act locally and cause smooth muscle contraction, increased vascular permeability, mucous gland secretion, and infiltration of inflammatory cells (neutrophils and eosinophils). However, histamine can also be released by non-IgE-mediated mechanisms (e.g., due to exposure to certain fungi). 463... 

Apelins and the Apelin Receptor. Figure 3 Scheme illustrating the hypothesised mechanisms of control of human (a) vasculartone and (b) cardiac contractility by apelin peptides ( ). In the vasculature, apelins (released via the small vesicles of the constitutive pathway) may act directly to activate apelin receptors on the underlying smooth muscle to produce vasoconstriction. This response may be modified by apelin peptides feeding back onto apelin receptors on endothelial cells to stimulate the release of dilators, such as nitric oxide. In heart, apelin peptides, released from endocardial endothelial cells, activate apelin receptors on cardiomyocytes to elicit positive inotropic actions. 

Bronchial Asthma. Figure 2 Mechanisms of bronchial hyperresponsiveness. Toxic products from eosinophils [cationic peptides, reactive oxygen species (ROS)] cause epithelial injury. Nerve endings become easily accessible to mediators from mast cells, eosinophils [eosinophil-derived neurotoxin (EDN)], and neutrophils, and to airborne toxicants such as S02. Activation of nerve endings stimulates effector cells like mucosal glands and airway smooth muscle either directly or by cholinergic reflexes. 

Prostacyclin (epoprostanol) is one of the few drugs effective for the treatment of Primary Pulmonary Hypertension (PPH) a rare but frequently fatal illness of young adults. Increased blood pressure in the pulmonary circulation leads to right-heart failure. Continuous infusion of epoprostanol leads to a decrease in blood pressure however, it is unclear whether this is due to direct dilator activity of the IP receptor acting on smooth muscle, or a more indirect mechanism. 

Similar Ca2+ release mechanism operates also in smooth muscles, neurons and some peripheral tissues. 

Smooth Muscle Tone Regulation. Figure 1 Mechanisms leading to agonist stimulated calcium-dependent and calcium-independent contraction of smooth muscle. NE, norepinephrine. See text for the other abbreviations. 

Smooth Muscle Tone Regulation. Figure 2 Membrane mechanisms leading to an increases in cytosolic calcium concentration, depolar, depolarisation of the membrane see text for abbreviations. 

Vasodilators are a group of dtugs, which relax the smooth muscle cells of the blood vessels and lead to an increased local tissue blood flow, a reduced arterial pressure and a reduced central venous pressure. Vasodilators reduce the cardiac pre-load as well as after-load and thereby reduce cardiac work. They are used in a variety of conditions including hypertension, cardiac failure and treatment/prevention of angina pectoris. Major groups are Ca2+-channel blockers (e.g. dihydropyridines), NO-donators (e.g. organic nitrates), K+-channel openers (minoxidil), phosphodiesterase inhibitors (e.g. sildenafil), Rho-kinase inhibitors (e.g. Y27632) or substances with unknown mechanism of action (e.g. hydralazine). Inhibitors of the... 

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