title: Models of cardiovascular disease: measurement of antihypertensive activity in the conscious rat (SHR, DOCA-salt, and Goldblatt hypertension models).
abstract: The protocols described in this unit are used to assess the effects of new chemical entities on hypertension in conscious rats. In the spontaneously hypertensive rat (SHR) model, the results obtained with the reference compounds clonidine, prazosin, propranolol, and captopril are provided for illustration. All compounds demonstrate antihypertensive activity, with captopril and prazosin being the least and the most active, respectively. In the deoxycorticosterone acetate (DOCA)-salt model in the rat, the test substance shown as an example (a potential endothelin ET(A)-receptor antagonist) prevents the development of hypertension in the first phase. However, the effects of treatment disappear in the very last phase of the study, suggesting the development of a malignant hypertension resistant to treatment in this model. In the Goldblatt hypertension rat model (renal artery stenosis), losartan prevents the development of hypertension. It does not modify the weight of the right and left kidneys but slightly reduces the degree of cardiac hypertrophy.
authors.affiliation: Porsolt and Partners Pharmacology, Boulogne-Billancourt, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Guillaume
authors.forename: Daniel
authors.initials: D
authors.lastname: Provost
authors.forename: Pamela
authors.initials: P
authors.lastname: Legrand
authors.forename: Michael
authors.initials: M
authors.lastname: Godes
authors.forename: Pierre
authors.initials: P
authors.lastname: Lacroix
mesh_terms: D000822:Animal Husbandry / Q000379:methods; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002985:Clinical Protocols; D003900:Desoxycorticosterone / Q000633:toxicity; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D006973:Hypertension / Q000188:drug therapy*; D006978:Hypertension, Renovascular / Q000188:drug therapy; D008026:Ligation; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D012077:Renal Artery; D013223:Statistics as Topic / Q000379:methods
chemical_list: D000959:Antihypertensive Agents; D003900:Desoxycorticosterone