Renal and myocardial adrenoceptors in steroid contraceptive-induced hypertension in rats
Geraghty, DP and Byrne, KB and McPherson, GA and Burcher, E, Renal and myocardial adrenoceptors in steroid contraceptive-induced hypertension in rats, Clinical and Experimental Physiology and Pharmacology, 17, (8) pp. 567-578. ISSN 0305-1870 (1990) [Refereed Article]
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.