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Renal and myocardial adrenoceptors in steroid contraceptive-induced hypertension in rats

journal contribution
posted on 2023-05-17, 05:41 authored by Dominic GeraghtyDominic Geraghty, Byrne, KB, McPherson, GA, Burcher, E
1. Systolic blood pressure (SBP), bodyweight, organ weight, renal beta-adrenoceptor and myocardial beta- and myocardial alpha 1-adrenoceptor characteristics were investigated in female Sprague-Dawley rats after chronic subcutaneous (s.c.) administration of ethynyloestradiol (EE2, 0.2 microgram/day), levonorgestrel (NG, 2.0 micrograms/day) separately and in combination (EE2/NG). 2. EE2 caused a sustained increase in SBP from 6 weeks (maximum at 14 weeks, +22 mmHg compared to control) which was accompanied by increased kidney and ventricle weight after 12 weeks. EE2/NG-treated rats also demonstrated a gradual rise in SBP (maximum at 9 weeks, +18 mmHg compared with control) with renal and ventricular hypertrophy, but were normotensive by week 17 of treatment. In contrast, NG induced only transient SBP increases (maxima at 5 and 10 weeks, +14 mmHg compared with control), unaccompanied by organ hypertrophy. Norethisterone (2 micrograms/day) also produced transient increases (weeks 6-8, +13 mmHg) in SBP. 3. alpha 1- and beta-adrenoceptors were investigated using [3H]-prazosin and (-)-[125I]-iodocyanopindolol (ICYP), respectively. Myocardial alpha 1- and beta-adrenoceptors were unaffected by steroid contraceptive administration for up to 12 weeks. Renal beta-adrenoceptor affinity was markedly reduced in 12 week EE2-treated rats (equilibrium dissociation constant, KD, 53 +/- 7 pmol/L) compared with controls (KD, 31 +/- 4 pmol/L), an effect which was prevented by co-administration of NG (KD, 34 +/- 8 pmol/L). Renal beta-adrenoceptor number was not altered by any treatment. 4. The relatively late onset of organ hypertrophy and beta-adrenoceptor changes appear to result from, rather than cause, EE2-induced hypertension.

History

Publication title

Clinical and Experimental Physiology and Pharmacology

Volume

17

Issue

8

Pagination

567-578

ISSN

0305-1870

Department/School

School of Health Sciences

Publisher

Blackwell Science

Place of publication

Australia

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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    University Of Tasmania

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