Renal and myocardial adrenoceptors in steroid contraceptive-induced hypertension in rats.
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.
Geraghty
D P
DP
Department of Biological Sciences, Deakin University, Victoria, Australia.
Byrne
K B
KB
McPherson
G A
GA
Burcher
E
E
D000818:Animals; D001667:Binding, Competitive; D001794:Blood Pressure / Q000187:drug effects; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects*; D006973:Hypertension / Q000139:chemically induced*; D020120:Iodocyanopindolol; D007668:Kidney / Q000187:drug effects*; D016912:Levonorgestrel; D009644:Norgestrel / Q000008:administration & dosage / Q000494:pharmacology*; D010869:Pindolol / Q000031:analogs & derivatives / Q000032:analysis; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D011943:Receptors, Adrenergic, beta; D009644:Norgestrel; D004997:Ethinyl Estradiol; D016912:Levonorgestrel; D020120:Iodocyanopindolol; D010869:Pindolol