Heart peptide hormones

Natriuretic peptides are a family of peptide hormones. All of them contain a 17-amino acid long ring that is closed by a disulfide bond between two cysteine residues. ANP (atrial natriuretic peptide) is mainly expressed in the atria of the heart, whereas BNP (B-type natriuretic peptide) is synthesized in the ventricular myocardium. CNP occurs mainly in the endothelium and is thought to have a paracrine function. ANF and BNF lower blood pressure by a direct effect on smooth muscle and on the salt retention in the kidney. Natriuretic peptides bind and activate particulate guanylyl cyclases. 

The epidermal growth factor (EGF) domain is one example of a module that is present in several proteins (Figure 3-8). EGF is a small, soluble peptide hormone that binds to cells in the embryo and in skin and connective tissue in adults, causing them to divide. It is generated by proteolytic cleavage between repeated EGF domains in the EGF precursor protein, which is anchored in the cell membrane by a membrane-spanning domain. EGF modules are also present in other proteins and are liberated by proteolysis these proteins include tissue plasminogen activator (TPA), a protease that is used to dissolve blood clots In heart attack victims ... 

A significant study using extracts of rat cardiac atrial tissue produced copious excretion of urine, Na+ and Cl- at levels 30 times above normal on being injected into rats. The discovery of a saluretic peptide hormone thus established the heart as an endocrine gland with strong effects on water and electrolyte balance (Na+ and Cl-). Now named Atrial Natriuretic Factor (ANF), it may be useful in treating CHF patients in whom levels have been shown to be increased, yet are associated with decreased cardiac output. The normal effect of ANF infusion is to increase water, Na+, and K+ excretion and inhibit it for aldosterone and cortisone. Most of these effects do not occur in CHF patients, which may be the reason for the edema accompanying CHF. Why that is, however, remains to be seen. When the reasons become known, it may be possible to find a way around the CHF patient s inability to respond to ANF. That should solve many problems. 

Historically the only melanocortin peptide to be used clinically is the parent hormone from which all these peptides are derived from namely ACTH (see above). It has also been used in the treatment infantile spasms for epilepsy, where it is administered as an intramuscular injection only over a 2-12 weeks period. Obvious side effects include weight gain, puffy face, high blood pressure and an increased risk of infection and should never be administered to patients with diabetics, renal or heart failure. ACTH is also used as a stimulation test to measure adrenal cortex activity, i.e. production of cortisol and is used to ascertain whether someone has Addison s disease. 

Atrial natriuretic peptide is released from myocardial cells in the atria of the heart in response to an increase in atrial filling, or an increase in plasma volume. This hormone inhibits the release of renin. With less angiotensin Il-induced vasoconstriction of the afferent arteriole, RBF, GFR, and urine output increase. The increased loss of water and solutes decreases blood volume toward normal. 

Physiologists had postulated for a long time about the existence of a sodium excreting hormone to prevent Na overload and consequent deleterious effects of high blood pressure on the heart and vascular system. At least two such natriuretic factors have been described atrial or A-type and brain or B-type natriuretic factors. Structurally, the natriuretic factors are peptides with a cysteine-cysteine disulfide bridge creating a characteristic loop , this is illustrated by Figure 8.8. 

While the angiotensins promote release of aldosterone, the atrial natriuretic hormoner aa cc inhibits release. This group of 21- to 33-residue polypeptides, secreted by cells of the atria (auricles) of the heart, also inhibits release of renin and promotes secretion of both Na+ and water. Thus, they antagonize the action of aldosterone, which promotes Na+ retention. However, there is uncertainty as to the significance of these peptides. The following metabolite of y-tocopherol (Fig. 15-24) has been isolated from urine and is proposed as a new endogenous natriuretic factor.dd... 

Physiologically, in both normal and hypertensive individuals, blood pressure is maintained by moment-to-moment regulation of cardiac output and peripheral vascular resistance, exerted at three anatomic sites (Figure 11-1) arterioles, postcapillary venules (capacitance vessels), and heart. A fourth anatomic control site, the kidney, contributes to maintenance of blood pressure by regulating the volume of intravascular fluid. Baroreflexes, mediated by autonomic nerves, act in combination with humoral mechanisms, including the renin-angiotensin-aldosterone system, to coordinate function at these four control sites and to maintain normal blood pressure. Finally, local release of hormones from vascular endothelium may also be involved in the regulation of vascular resistance. For example, nitric oxide (see Chapter 19 Nitric Oxide, Donors, Inhibitors) dilates and endothelin-1 (see Chapter 17 Vasoactive Peptides) constricts blood vessels. 

Hormones are secreted by specialized glands (adrenal, hypothalamus, ovary, pancreas, parathyroid, pineal, pituitary, testes, thyroid) or other tissues (e.g., heart, gut, and kidney), and regulate the cellular activities of distant tissues. Plasma levels of hormones are tightly regulated through homeostatic feedback systems. The peptide and protein hormones typically have short half-lives (minutes), which allow rapid changes in plasma levels and rapid enhancement or attenuation of their biological effects. 

Atrial natriuretic hormone (peptide) Heart Kidneys Increase Na+ excretion... 

Angiotensin II is an octapeptide, which was initially described as a potent vasoconstrictor agent. However, its functions have since been expanded to include regulation of cell growth, inflammation, electrolyte and water balance, hormone secretion, sympathetic nervous system activity, differentiation, and apoptosis. The discovery that it is produced both systemically and locally was instrumental in establishing a pivotal role for the peptide in several disease states, including hypertension, coronary heart disease, myocarditis, congestive heart failure, atherosclerosis, and nephrosclerosis. 

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