1. Systolic blood pressure (SBP), bodyweight, organ weight, renal P-adrenoceptor and myocardial P-and myocardial al-adrenoceptor characteristics were investigated in female Sprague-Dawley rats after chronic subcutaneous (s.c.) administration of ethynyloestradiol (EE2, 0.2 pg/day), levonorgestrel (NG, 2.0 pg/day) separately and in combination (EE2/ NG).2. EE2 caused a sustained increase in SBP from 6 weeks (maximum at 14 weeks, 4-22 mmHg compared to control) which was accompanied by increased kidney and ventricle weight after 12 weeks. EEz/NG-treated rats also demonstrated a gradual rise in SBP (maximum at 9 weeks, 4-18 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 pg/ day) also produced transient increases (weeks 6-8, 4-13 mmHg) in SBP.
011-and P-adrenoceptors were investigated using [3H]-prazosin and (-)-[1251]-iodocyanopindolol (ICY P), respectively. Myocardial a~-and P-adrenoceptors were unaffected by steroid contraceptive administration for up to 12 weeks. Renal 6-adrenoceptor affinity was markedly reduced in 12 week EEz-treated rats (equilibrium dissociation constant, KD, 53 f 7 pmol/ L) compared with controls (KD, 31 f4 pmol/L), an effect which was prevented by co-administration of NG (KD, 34 f 8 pmol/ L). Renal P-adrenoceptor number was not altered by any treatment.4. The relatively late onset of organ hypertrophy and P-adrenoceptor changes appear to result from, rather than cause, EEz-induced hypertension.