Abstract: 309

MODULATION OF ANGIOTENSIN II RESPONSES ON THE UTERINE ARCUATE ARTERY BY AT-1R, AT-2R AND BK-2R (BRADYKININ) RECEPTOR BLOCKADE DURING PREGNANCY IN THE RAT.

Jean St-Louis¹ , Benoît Sicotte¹ , Michèle Brochu¹
Research Center, Hôpital Ste-Justine, Montréal, Québec, Canada ¹

Uterine circulation undergoes important structural and functional changes in pregnancy. We investigated the influence of blockade of angiotensin II (AngII) receptor (AT-2R) and bradykinin (BK) receptor (BK-2R) on responses of the uterine circulation to AngII. Uterine arcuate arteries (diam. 120-200 µm) from virgin and term-pregnant were setup in wire myographs under a passive tension equivalent to a transmural pressure of 50 mmHg. Concentration-response (CR) curves to AngII (1 nM to 1 µM) with and without Losartan (0.1 µM; AT-1R blocker) were measured in the absence and presence of PD123319 (AT-2R blocker, 0.1 µM) or HOE-140 (BK-2R blocker, 1.0 µM). Pregnancy increased, under all conditions tested, AngII responses in arcuate arteries. Maximum responses (E_MAX) to AngII were also increased in arteries bathed with PD123319 or HOE-140 in both groups. For instance, in virgin rats, E_MAX to AngII increased from 1.52 ± 0.19 to 2.07 ± 0.05 and 2.11 ± 0.17 mN/mm with PD123319 or HOE-140, respectively (P<0.01). Losartan (0.1 µmol/L) antagonized the responses to AngII in all groups of vessels. In the absence of the other antagonists, it produced a parallel right shift of the CR curve to AngII, that was of a lower magnitude in arteries of pregnant rats. In the presence of AT-2R or BK-2R blockers, the right shift was no longer parallel in both groups, since E_MAX was smaller in the presence of the AT-1R antagonist. Nevertheless, the antagonist effect of Losartan was still reduced in arcuate arteries of pregnant than of virgin rats. These data show that AngII responses in uterine arcuate arteries of the rat is mediated by the AT-1R receptor. However, this response appeared to be modulated by an interaction with AT-2R and BK-2R receptors. Finally, potency of Losartan to block responses of AngII decreased in the arcuate arteries of pregnant rats.

    This abstract is being presented on Monday, August 2 at 8:00 AM to 10:15 AM at CUB 2nd Floor Ballroom.