1 / 29

Vasoactive peptides

Vasoactive peptides. By S.Bohlooli, PhD. Vasoconstrictors: Angiotensin II Vasopressin Endothelins Neuropeptide Y urotensin. Vasodilators: Bradykinin Natriuetic peptids Vasoactive intestinal peptide Substance P Neurotensin Calcitonin gene related peptide adernomedullin.

annanorris
Download Presentation

Vasoactive peptides

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Vasoactive peptides By S.Bohlooli, PhD

  2. Vasoconstrictors: Angiotensin II Vasopressin Endothelins Neuropeptide Y urotensin Vasodilators: Bradykinin Natriuetic peptids Vasoactive intestinal peptide Substance P Neurotensin Calcitonin gene related peptide adernomedullin Vasoactive peptides

  3. Angiotensin • Biosynthesis • Renin and factors controlling renin secretion • Renal vascular receptor • Macula Densa • Sympathetic nervous system • Angiotensin • Pharmacologic alteration of renin release

  4. Formation of angiotensin peptides

  5. Actions of Angiotensin II • Blood pressure: arteriolar • Adrenal cortex: aldosterone biosynthesis • Kidney: renal vasoconstrictor, sodium reabsorption • Central nervous system: dipsogenic effect, vasopressin, ACTH  • Cell growth: mitogenic

  6. Angiotensin receptors & mechanism of action • AT1 • AT2

  7. Multiple mechanisms of AT1 receptor-effector coupling

  8. Inhibition of the renin angiotensin system • Block of renin secretion: • clonidine and propranolol • Renin inhibitors: • Aliskiren ,remikiren, enalkiren • Converting enzyme inhibitors • Captopril and enalapril • Angiotensin antagonists: AT1 • Losartan , valsartan

  9. Kinins • Biosynthesis • Kallikreins • Kininogens • Formation of kinins in plasma & tissues

  10. the kallikrein-kinin and renin-angiotensin systems.

  11. Structure kinin agonsits & antagonists

  12. Actions of kinins • Cardiovascular system • arteriodilator, venoconstrictor • Endocrine & exocrine glands • Pancreas, kidney, intestine, salivary glands • Inflammation • Redness, local heat, swelling, pain • Sensory nerves • Pain producing substance

  13. Kinin receptors & mechanism of action • B1: inflammatory response, collagen synthesis, cell multiplication • B2 • B2A • B2B

  14. Drugs affecting the kallikrein kinin system • Icatibant: antagonist of B2, oral • Aprotinin: kallikrein inhibitor

  15. Vasopressin • Long term control of blood pressure • Water reabsorption • Short term control of blood pressure • Vasoconstrictor

  16. Vasopressin receptor agonists

  17. Vasopressin receptors & antagonists

  18. Natriuretic peptides • ANP: arterial natriuretic peptide • BNP: brain natriuretic peptide • CNP: c-type natriuretic peptide

  19. Structures

  20. Pharmcodynamics & pharmcokinetics • ANPA • coupled to guanylyl cyclase • ANPB • coupled to guanylyl cyclase • ANPC • BNP as nesiritide

  21. Vasopeptidase inhibitors • Inhibits two metalloprotease enzymes • NEP 24.11 and ACE • Increase level of natriutetic peptides and decreased formation of angiotensin II • Omapatrilat, sampatrilat, fasidotrilat

  22. Endothelins • Potent vasoconstrictor peptides • 3 isoforms were identified: • ET-1, ET-2, ET-3 • 21-amino-acid peptide • Receptors: ETA, ETB

  23. Structures of the endothelin

  24. Endothelins: actions • Dose dependent vasoconstriction • Coronary, kidney • Potent constriction of tracheal and bronchial smooth muscle • Endocrine system: increased secrestion of renin, aldosterone, vasopressin, atrial natriuretic peptide • Potent mitogen of vascular smooth muscle

  25. Generation of endothelin-1 (ET-1) in the vascular endothelium

  26. Inhibitors of endothelin synthesis and action • Receptor antagonists • nonselective antagonist • Bosentan: has been associated with fatal hepatotoxicity • ETA-selective antagonists : • sitaxentan, ambrisentan • Endothelin converting enzyme inhibitors • Phosphoramidon

  27. Effects of endothelin antagonists • Vasodilation • Potentail use: • Heart failure, pulmonary hypertension • Essential hypertension, atherosclerosis • Myocardial infarction , cardiac hypertrophy

  28. Substance P • Belongs to tachykinin family: • Neurokinin A , Neurokinin B • Substance P • Actions: anxiety, depression, nausea, emesis • Effect on smooth muscle: artriodilator, venoconstrictor • Receptors: NK1, NK2, NK3 • Receptor Antagonists: aprepitant

More Related