| Antihypertensive effects of an aromatase inhibitor in inbred salt-sensitive rats. | |
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MedLine Citation:
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PMID: 2045138 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Rats susceptible to the hypertensive effect of dietary salt (SS/Jr) have excess urinary 19-nordeoxycorticosterone compared with salt-resistant control rats (SR/Jr). 19-Nordeoxycorticosterone is a hypertensinogenic mineralocorticoid, but whether it contributes to the salt sensitivity of SS/Jr is unknown. This study sought to evaluate the contribution of 19-nordeoxycorticosterone to the salt sensitivity of SS/Jr by lowering its production with an aromatase inhibitor, 10-propargyl-androst-4-ene,3,17-dione (19-acetylenic-androstenedione, 19-AA). This aromatase inhibitor also preferentially inhibits nonaromatizing adrenal 19-hydroxylation, an essential step in the formation of 19-nordeoxycorticosterone. To test this hypothesis, inhibitor (120 mg) or vehicle pellets were implanted into male and female weanling SS/Jr at 42 days of age. A high salt diet (8% NaCl) was started and two additional pellets were implanted at 52 and 62 days of age. Systolic blood pressure was measured in all animals and urinary corticosteroids in males. Compared with vehicle, the inhibitor lowered blood pressure at 50 days of age (when it could first be measured) until 64 days of age in females and 71 days of age in males. Corticosterone and aldosterone levels were not different between 19-AA- and vehicle-treated SS/Jr. 19-Nordeoxycorticosterone levels, however, were mildly reduced with the inhibitor (0.05 less than p less than 0.10). After 28 days of high salt diet all 23 of the 19-AA-treated SS/Jr were alive, whereas almost one half of the control animals had died. These data demonstrate that 19-AA attenuates the hypertension in SS/Jr; this effect may be through reduction in 19-nordeoxycorticosterone production.(ABSTRACT TRUNCATED AT 250 WORDS) |
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Authors:
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G T Griffing; J C Melby; M Holbrook; O N Johnston |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Hypertension Volume: 17 ISSN: 0194-911X ISO Abbreviation: Hypertension Publication Date: 1991 Jun |
Date Detail:
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Created Date: 1991-07-12 Completed Date: 1991-07-12 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 771-5 Citation Subset: IM |
Affiliation:
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Evans Memorial Department of Clinical Research, University Hospital, Boston University Medical Center, MA 02118. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aldosterone
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urine Androstenedione / analogs & derivatives, pharmacology Animals Antihypertensive Agents / pharmacology* Aromatase Inhibitors* Cortisone / urine Desoxycorticosterone / analogs & derivatives*, pharmacology, urine Female Hypertension / prevention & control* Male Pargyline / analogs & derivatives, pharmacology Rats Rats, Inbred Strains Sodium Chloride / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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HL-40123-01A1/HL/NHLBI NIH HHS; R37DK12027-20/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antihypertensive Agents; 0/Aromatase Inhibitors; 4682-70-6/19-nordeoxycorticosterone; 52-39-1/Aldosterone; 53-06-5/Cortisone; 555-57-7/Pargyline; 63-05-8/Androstenedione; 64-85-7/Desoxycorticosterone; 7647-14-5/Sodium Chloride; 77016-85-4/plomestane |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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