Lec 10-1 Vasoactive Peptides PDF

L10 Dr. Alaa AL- Sheek Mashhad Vasoactive peptides: They are used by most tissues for cell-to-cell communication. They play important roles in the autonomic and central nervous systems. These peptides include Vasoconstrictors (angiotensin II, va...

L10 Dr. Alaa AL- Sheek Mashhad Vasoactive peptides: They are used by most tissues for cell-to-cell communication. They play important roles in the autonomic and central nervous systems. These peptides include Vasoconstrictors (angiotensin II, vasopressin, endothelins, neuropeptide Y, and urotensin) Vasodilators (bradykinin and related kinins, natriuretic peptides, vasoactive intestinal peptide, substance P, neurotensin, calcitonin gene- related peptide, and adrenomedullin). Angiotensin ii: It formed by enzymatic cleavage of angiotensin I from angiotensinogen by renin which is synthesized by juxtaglomerular cells, then conversion of angiotensin I to angiotensin II by converting enzyme. Actions of Ang II: It is a very potent pressor agent (40 times more potent than NE). Stimulate aldosterone biosynthesis. It induces renal vasoconstriction, increase proximal tubular sodium reabsorption, and inhibit the secretion of renin. Stimulate drinking (dipsogenic effect) 1  Mitogenic for vascular and cardiac muscle cells and may contribute to the development of cardiovascular hypertrophy. Clinical applications: Aliskiren: produces a dose-dependent reduction in plasma renin activity and causes dose-related reductions in blood pressure. ACE inhibitors: (captopril, enalapril, Lisinopril…etc) they decrease systemic vascular resistance without increasing heart rate. 2  Angiotensin Receptor Antagonists (Losartan, valsartan, candesartan, and telmesartan) are orally active, potent, and specific competitive antagonists of angiotensin AT2 receptors. 3 Vasopressin: (anti diuretic hormone, ADH): Has long-term control of blood pressure through its action on the kidney to increase water re- absorption (V2 receptors) and short-term regulation of arterial pressure by its vasoconstrictor action (V1 receptors). Used for nocturnal enuresis in children over 5 years as a nasal spray. Conivaptan is an antagonist of vasopressin (V1 receptors) used for the treatment of hypertension and heart failure. Endothelins: They are a potent vasoconstrictor peptides produced mainly by vascular endothelium. They cause dose-dependent vasoconstriction in most vascular beds. Endothelins also exert direct positive inotropic and chronotropic actions on the heart and are potent coronary vasoconstrictors. 4 On the kidneys, it causes vasoconstriction and decrease glomerular filtration rate and sodium and water excretion. In the respiratory system, they cause potent contraction of tracheal and bronchial smooth muscle. Clinical applications: Bosentan is a nonselective antagonist. This drug is active intravenously and orally. Treat pulmonary hypertension by decreasing pulmonary vascular resistance and dyspnea. Bosentan is given orally, well tolerated but 11% of patients shown increase serum aminotransferase levels. So, liver function test monitored at baseline & then monthly. In animal studies, bosentan causes major birth defects if used in pregnancy, so CI in pregnancy. Vasoactive intestinal peptide: It functions as a neurotransmitter or neuromodulator and produces marked vasodilation in most vascular beds and exerts positive inotropic and chronotropic effects. 5 Substance p: It is a neurotransmitter and in the gastrointestinal tract, where it may play a role as a transmitter in the enteric nervous system and as a local hormone. It is a potent arteriolar vasodilator, producing marked hypotension Clinical applications: Aprepitant: it is receptor antagonists. It is highly selective and orally active, useful in preventing chemotherapy-induced emesis. Calcitonin gene-related peptide (cgrp): It causes hypertension and suppression of feeding when injected centrally. It causes hypotension and tachycardia when given peripherally. It plays a central role in the pathophysiology of migraine. Urotensin: It is a potent constrictor of vascular smooth muscle Nitric Oxide (endothelium-derived relaxing factor): 6 It is a gaseous signaling molecule that readily diffuses across cell membranes and regulates a wide range of physiologic and pathophysiologic processes including cardiovascular, inflammation, immune, and neuronal functions with main vasodilatation effect. 7