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The effect of isosorbide dinitrate on uterine and ovarian blood flow during oestrous cycle and early pregnancy in mares
Journal of Equine Veterinary Science 34 (2014) 167
Contents lists available at ScienceDirect
Journal of Equine Veterinary Science journal homepage: www.j-evs.com
The effect of isosorbide dinitrate on uterine and ovarian blood flow during oestrous cycle and early pregnancy in mares D. Zoller, J. Lüttgenau, H. Bollwein Clinic of Reproductive Medicine, Vetsuisse-Faculty University of Zurich
It has been proposed that in mares fertility could be affected by uterine blood flow [Blaich U,et.al,. Pferdeheilkunde 1999;15:547-50].An adequate blood supply is essential for hormonal signalling, uterine contractility, placentation and feto-endometrial interactions (Le Blanc MM, Causey RC. Reprod Domest Anim 2009;44:11-22.The objective of this study was to investigate the effects of the exogenous application of the vasodilator nitric oxide donor isosorbide dinitrate (ISDN) on uterine and ovarian perfusion in cycling mares and early pregnant mares by using transrectal Doppler ultrasonography. Six Trotter mares, aged 7 to 14 years were examined daily during three oestrous cycles. Four of these mares were additionally examined during early pregnancy. Mares were treated with placebo (lactose 60 mg), a low dose of ISDN (30 mg) and a high dose of ISDN (60 mg) orally (one treatment per cycle, in random order) every 12 h from Day 1 to 11 of the cycle (Day 0 ¼ day of ovulation following prostaglandin-induced luteolysis). Four of these mares were additionally treated with a placebo (lactose 60 mg) or ISDN (60 mg) orally every 12 h from Day 1 to 11 after insemination. The uterine and ovarian blood supplies were studied by Doppler ultrasonography of both uterine arteries and both ovarian arteries once a day
0737-0806/$ – see front matter Ó 2014 Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jevs.2013.10.122
immediately prior to oral treatment starting on Day 1. Blood flow resistance was determined semi-quantitatively using the pulsatility index (PI) and plasma progesterone concentrations were determined with an enzyme immunoassay. Mean PI values of both uterine arteries and PI values of the dominant ovarian artery were lower (P<0.05) and the mean concentration of plasma progesterone higher (P<0.0001) after administration of ISDN 30 as well as ISDN 60 compared to placebo cycles. No differences (P>0.05) occurred in mean PI values of both uterine arteries between placebo pregnancies and ISDN 60 pregnancies, ISDN 30- and ISDN 60 cycles, but their mean PI values were lower (P<0.05) compared to placebo cycles. During ISDN 60 pregnancies only PI values in the dominant ovarian artery decreased (P<0.05) compared to placebo pregnancies. There was no difference between mean PI values of the dominant ovarian artery in the ISDN 60 pregnancies and the ISDN 60 cycles (P>0.05). Plasma progesterone concentrations were higher (P<0.05) during ISDN 60 pregnancies compared to placebo pregnancies. In conclusion, ISDN affects genital perfusion in cycling as well as in early pregnant mares. If the rise in genital perfusion has an effect on fertility has to be investigated in further studies.
Contents lists available at ScienceDirect
Journal of Equine Veterinary Science journal homepage: www.j-evs.com
The effect of isosorbide dinitrate on uterine and ovarian blood flow during oestrous cycle and early pregnancy in mares D. Zoller, J. Lüttgenau, H. Bollwein Clinic of Reproductive Medicine, Vetsuisse-Faculty University of Zurich
It has been proposed that in mares fertility could be affected by uterine blood flow [Blaich U,et.al,. Pferdeheilkunde 1999;15:547-50].An adequate blood supply is essential for hormonal signalling, uterine contractility, placentation and feto-endometrial interactions (Le Blanc MM, Causey RC. Reprod Domest Anim 2009;44:11-22.The objective of this study was to investigate the effects of the exogenous application of the vasodilator nitric oxide donor isosorbide dinitrate (ISDN) on uterine and ovarian perfusion in cycling mares and early pregnant mares by using transrectal Doppler ultrasonography. Six Trotter mares, aged 7 to 14 years were examined daily during three oestrous cycles. Four of these mares were additionally examined during early pregnancy. Mares were treated with placebo (lactose 60 mg), a low dose of ISDN (30 mg) and a high dose of ISDN (60 mg) orally (one treatment per cycle, in random order) every 12 h from Day 1 to 11 of the cycle (Day 0 ¼ day of ovulation following prostaglandin-induced luteolysis). Four of these mares were additionally treated with a placebo (lactose 60 mg) or ISDN (60 mg) orally every 12 h from Day 1 to 11 after insemination. The uterine and ovarian blood supplies were studied by Doppler ultrasonography of both uterine arteries and both ovarian arteries once a day
0737-0806/$ – see front matter Ó 2014 Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jevs.2013.10.122
immediately prior to oral treatment starting on Day 1. Blood flow resistance was determined semi-quantitatively using the pulsatility index (PI) and plasma progesterone concentrations were determined with an enzyme immunoassay. Mean PI values of both uterine arteries and PI values of the dominant ovarian artery were lower (P<0.05) and the mean concentration of plasma progesterone higher (P<0.0001) after administration of ISDN 30 as well as ISDN 60 compared to placebo cycles. No differences (P>0.05) occurred in mean PI values of both uterine arteries between placebo pregnancies and ISDN 60 pregnancies, ISDN 30- and ISDN 60 cycles, but their mean PI values were lower (P<0.05) compared to placebo cycles. During ISDN 60 pregnancies only PI values in the dominant ovarian artery decreased (P<0.05) compared to placebo pregnancies. There was no difference between mean PI values of the dominant ovarian artery in the ISDN 60 pregnancies and the ISDN 60 cycles (P>0.05). Plasma progesterone concentrations were higher (P<0.05) during ISDN 60 pregnancies compared to placebo pregnancies. In conclusion, ISDN affects genital perfusion in cycling as well as in early pregnant mares. If the rise in genital perfusion has an effect on fertility has to be investigated in further studies.