title: Hypotensive agents from snake venoms.
abstract: Many snake venoms contain toxins which produce profound cardiovascular effects. The site of action of these toxins includes cardiac muscle, vascular smooth muscle and the capillary vascular bed. Some snake venoms, for example, contain peptides that inhibit angiotensin converting enzyme and potentiate the biological actions of bradykinin. Other snake venoms contain structural and functional equivalents of mammalian natriuretic peptides. Sarafotoxins are short peptide toxins found in the venoms of snakes from Atractaspis spp. which display potent vasoconstriction properties. These peptides, which share a high degree of sequence identity with endothelins, recognize and bind to endothelin receptors. Snakes have also evolved toxins which block L-type Ca(2+) currents (eg. calciseptine, FS2 toxins, C(10)S(2)C(2) and S(4)C(8)). Snake venom proteins have also been shown to increase vascular permeability. One such protein, increasing capillary permeability protein (ICPP) has recently been isolated from the venom of Vipera lebetina. ICPP is an extremely potent permeability factor with a structure similar to vascular endothelial growth factor (VEGF). Thus there is a vast array of snake toxins with potent cardiovascular activity. Some of these proteins and peptides have proven to be highly selective tools in the study of physiological processes. Others have been used as probes of potential therapeutic targets or as lead compounds in the development of therapeutic agents. Therefore these and other related snake venom proteins hold great promise in the future understanding and treatment of cardiovascular diseases.
authors.affiliation: Department of Biological Sciences, National University of Singapore, Science Drive 4, Singapore 117543.
authors.forename: Roy
authors.initials: R
authors.lastname: Joseph
authors.forename: Susanta
authors.initials: S
authors.lastname: Pahari
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Hodgson
authors.forename: R Manjunatha
authors.initials: RM
authors.lastname: Kini
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001920:Bradykinin / Q000819:agonists; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology; D002986:Clinical Trials as Topic; D003435:Crotalid Venoms / Q000737:chemistry; D016232:Endothelins / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D045265:Natriuretic Peptides / Q000494:pharmacology; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology; D012910:Snake Venoms / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014757:Viper Venoms / Q000737:chemistry
chemical_list: D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D003435:Crotalid Venoms; D016232:Endothelins; D045265:Natriuretic Peptides; D009842:Oligopeptides; D012910:Snake Venoms; D014757:Viper Venoms; C006791:bradykinin potentiating factors; D001920:Bradykinin