Smooth muscle vasopressin effects

ANPs play an important role in the maintenance of cardiovascular homeostasis by counterbalancing the renin—angiotensin (RAS) system. ANP, the main circulating form of the natriuretic peptides, effectively relaxes vascular smooth muscle, promotes the excretion of sodium and water, and in the CNS inhibits vasopressin release and antagonizes AT-II induced thirst. 

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. 

Peptides are used by most tissues for cell-to-cell communication. As noted in Chapters 6 and 21, they play important roles in the autonomic and central nervous systems. Several peptides exert important direct effects on vascular and other smooth muscles. These peptides include vasoconstrictors (angiotensin II, vasopressin, endothelins, neuropeptide Y, and urotensin) and vasodilators (bradykinin and related kinins, natriuretic peptides, vasoactive intestinal peptide, substance P, neurotensin, calcitonin gene-related peptide, and adrenomedullin). This chapter focuses on the smooth muscle actions of the peptides. 

The chief hormones of the iteurohypophysis are the polypeptides oxytocin and vasopressin. The hormone characteristic of the pars intermedia Is the melanocyte-stimulating hormone. It is usually spoken of in the plural, since in most mammals both alpha and beta forms are known. The structures of the liist two arc shown In the Table I. The most prominent effect of oxytocin is the contraction ot smooth muscle, especially of the uterus, It also has a major effect upon the muscles about ihe breast, and so stimulates the ejection of milk in I,totaling animals. It has a delinile stimulating effect upon (he muscles of Ihe ureter, urinary bladder, intestine, and gall bladder. 

Vasopressin [vay soe PRESS in] (antidiuretic hormone, ADH), is structurally related to oxytocin (Figure 25.5). The chemically-synthesized nonapeptide has replaced that extracted from animal posterior pituitaries. Vasopressin has both antidiuretic and vasopressor effects. In the kidney it binds to the V2 receptor to increase water permeability and resorption in the collecting tubules. Thus the major use of vasopressin is to treat diabetes insipidus. It also finds use in controlling bleeding due to esophageal varices or colonic diverticula. Other effects of vasopressin are mediated by the Vi receptor, found in vascular smooth muscle, liver and other tissues. As might be expected the major toxicity is water intoxication and hyponatremia. Headache, bronchoconstriction and tremor also can occur. Caution must be used in treating patients with coronary artery disease, epilepsy and asthma. 

Most adverse effects are mediated through the Vj receptor acting on vascular and GI smooth muscle consequently, such adverse effects are much less common, and less severe, with desmopressin than with vasopressin. After the injection of large doses of vasopressin, marked facial pallor owing to cutaneous vasoconstriction is observed commonly. Increased intestinal activity is likely to cause nausea, belching, cramps, and an urge to defecate. Most serious, however, is the effect on the coronary circulation. Vasopressin should be administered only at low doses and with... 

Bradykinin, vasopressin, and oxytocin are peptide hormones. They are all nonapeptides. Bradykinin inhibits the inflammation of tissues. Vasopressin controls blood pressure by regulating the contraction of smooth muscle. It is also an antidiuretic. Oxytocin induces labor in pregnant women and stimulates milk production in nursing mothers. Vasopressin and oxytocin both have an intrachain disulfide bond, and their C-terminal amino acids contain amide rather than carboxyl groups. Notice that the C-terminal amide group is indicated by writing NH2 after the name of the C-terminal amino acid. In spite of their very different physiological effects, vasopressin and oxytocin differ only by two amino acids. 

Unlike vasopressin, desmopressin has significantly less effect on vascular smooth muscle. Vasoconstriction is less pronounced. 

At high concentrations, vasopressin stimulates contraction of smooth muscle in the uterus ("via oxytocin receptors) and GI tract ("via V receptors). Vasopressin is stored in platelets, and activation of Vj receptors stimulates platelet aggregation. Also, activation of V receptors on hepato-cytes stimulates glycogenolysis. The physiological significance of these effects of vasopressin in not known. 

ARBs potently and selectively inhibit most of the biological effects of Angll, including Angll-induced (1) contraction of vascular smooth muscle, (2) rapid pressor responses, (3) slow pressor responses, (4) thirst, (5) vasopressin release, (6) aldosterone secretion, (7) release of adrenal catecholamines, (8) enhancement of noradrenergic neurotransmission, (9) increases in sympathetic tone, (10) changes in renal function, and (11) cellular hypertrophy and hyperplasia. 

B. Vasopressin (Antidiuretic Hormone, ADH) Vasopressin is synthesized in the supraoptic nuclei of the hypothalamus and released from the posterior pituitary. As discussed in Chapter 15, vasopressin acts on V2 receptors and increases the synthesis or insertion of water channels by a cAMP-dependent mechanism, resulting in an increase in water permeability in the collecting tubules of the kidney. The increased water permeability permits water reabsorption into the hypertonic renal papilla, thus causing the antidiuretic effect. Vasopressin also causes smooth muscle contraction (a V, effect). Desmopresan, a selective agonist of V2 receptors, is used in the treatment of pituitary diabetes insipidus. 

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