Pretreatment of male guinea pigs by 17-beta-estradiol induces hypersensitivity of beta-adrenoceptors in electrically driven left atria.
BACKGROUND
It is well known that estrogen can modulate distribution and function of adrenergic receptors in the heart of different species. We reported here gender differences in adrenergic responsiveness of electrically driven guinea pig left atria.


METHODS
Experiments were performed on the guinea pigs divided in four groups: males control (MC), males treated by 17-beta-estradiol (MTE), females control (FC) and females treated by tamoxifen (FTT). After two weeks of treatment, the animals were sacrificed, the left atria were isolated and force of contraction (Fc), velocity of contraction (+dF/dt), velocity of relaxation (-dF/dt) and time to peak contraction (ttp) and relaxation time at 10% of amplitude (tt(10) ) were measured.


RESULTS
Apart from significantly lower Fc and longer tt10 in FC (0.97+/-0.12 mN, 233+/-7 ms, respectively) vs. MC (1.66+/-0.3, 176.3+/-18 ms, respectively, n=6, P<0.05), isoprenaline (ISO) and noradrenaline (NOR) (in the presence of prazosine) concentration-response curves were strongly shifted leftward in comparison with male group. Additionally, the maximal effects of. NOR was significantly lower in FC (about 40%) than in MC. Application of 17-beta-estradiol to males and tamoxifen to females guinea pigs confirmed crucial role of estrogen in observed phenomenon.


CONCLUSIONS
Our results indicate that estrogen not only downregulates beta1-adrenoceptors, but induces its hypersensitivity to catecholamines, at least in guinea pig left atria.
Kocić
Ivan
I
Department of Toxicology and Clinical Pharmacology, Inter-Faculty Institute of Maritime and Tropical Medicine, Powstania Styczniowego 9b, 81-519 Gdynia, Poland. ikocic@amg.gda.pl
Gruchała
Marta
M
Petrusewicz
Jacek
J
D000818:Animals; D016279:Atrial Function, Left / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004958:Estradiol / Q000008:administration & dosage*; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012727:Sex Characteristics
D011943:Receptors, Adrenergic, beta; D004958:Estradiol; D009638:Norepinephrine