Antihypertensive effect of 19-acetylenic-deoxycorticosterone in inbred salt-sensitive rats.
Rats susceptible to the hypertensive effect of dietary salt (SS/Jr) have excess 19-nor-deoxycorticosterone (19-nor-DOC) compared with salt-resistant control rats (SR/Jr). 19-Nor-deoxycorticosterone is a hypertensinogenic mineralocorticoid believed to contribute to the salt sensitivity of SS/Jr. 19-Acetylenic-deoxycorticosterone (19-Ac-DOC), an inhibitor of 19-nor-DOC biosynthesis, was evaluated for its antihypertensive effect in 20 hypertensive female SS/Jr rats. At 60 days of age, the rats were started on a high-salt diet (8% NaCl); then, at 120 days, the 10 surviving rats were divided into two groups. Group 1 included five animals with blood pressure +/- standard error (BP +/- SE) of 208 +/- 2 mm Hg that had 19-Ac-DOC implants (1 mg released over 10 days). Group 2 consisted of five animals with a BP of 204 +/- 2 mm Hg that had placebo implants (vehicle only). At 130 days, when another set of pellets was implanted, four rats were still alive in group 1 (BP 165 +/- 5 mm Hg) and none in group 2. At 140 days, the four surviving rats had a BP of 157 +/- 2 mm Hg. Finally, at 150 days, after 10 days off any 19-Ac-DOC, only two rats remained alive (BP 200 +/- 0 mm Hg). Urinary corticosterone +/- SE, DOC +/- SE, and 19-nor-DOC +/- SE before the first implant were 10 +/- 3, 16 +/- 5, and 42 +/- 14 micrograms/week, respectively, and 7 +/- 2, 13 +/- 5, 23 +/- 13 micrograms/week, respectively, after the second implant.(ABSTRACT TRUNCATED AT 250 WORDS)
Azar
S T
ST
Evans Memorial Department of Clinical Research, University Hospital, Boston, Massachusetts.
Melby
J C
JC
Griffing
G T
GT
Johnston
J O
JO
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D003900:Desoxycorticosterone / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000494:pharmacology; D004032:Diet; D004343:Drug Implants; D004351:Drug Resistance; D005260:Female; D006973:Hypertension / Q000139:chemically induced / Q000401:mortality; D051381:Rats; D011922:Rats, Mutant Strains; D012965:Sodium Chloride / Q000008:administration & dosage / Q000494:pharmacology*; D016019:Survival Analysis
D000959:Antihypertensive Agents; D004343:Drug Implants; C076838:19-acetylenic-deoxycorticosterone; D003900:Desoxycorticosterone; D012965:Sodium Chloride; C019026:19-nordeoxycorticosterone