Mirabito Colafella Katrina M, Samuel Chrishan S, Denton Kate M
Cardiovascular Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Australia.
Department of Physiology, Monash University, Melbourne, Australia.
Clin Sci (Lond). 2017 Nov 28;131(23):2795-2805. doi: 10.1042/CS20171225. Print 2017 Dec 1.
Relaxin is increasingly being recognized as a potent vasodilatory and antifibrotic hormone. Given that relaxin is present in the circulation during the luteal phase of the menstrual cycle and during pregnancy, when arterial pressure is lowest in women, relaxin may contribute to the relative cardiovascular protection observed in premenopausal women as compared with age-matched men and postmenopausal women. In the present study, we investigated the contribution of relaxin to the normal regulation of arterial pressure in adult female and male mice and during pregnancy. Mean arterial pressure (MAP) was measured via radiotelemetry in 14-week-old male and female wild-type (WT; C67BL/6xSv129) and relaxin knockout (KO) mice. Thereafter, female mice were time-mated with a (non-telemetered) male of the same genotype and MAP was measured throughout gestation. Basal MAP was ∼10 mmHg lower in WT females than males (<0.05). Relaxin deficiency increased basal MAP in females (<0.05 vs WT female), but not males. As expected, MAP decreased during gestation in WT mice. Conversely, in relaxin KO mice, arterial pressure increased during mid and late gestation (<0.05 as compared with WT). Moreover, relaxin deficiency impaired gestational weight gain and reduced litter size. This is the first study to (i) demonstrate that relaxin contributes to the sexual dimorphism of arterial pressure in mice and (ii) document the changes in the arterial pressure profile of pregnant relaxin KO mice. Understanding the mechanisms that underlie the regulation of arterial pressure in premenopausal females may uncover new strategies to treat hypertension in women (non-pregnant and pregnant) and men.
松弛素越来越被认为是一种强大的血管舒张和抗纤维化激素。鉴于在月经周期的黄体期和怀孕期间，女性动脉压最低时，松弛素存在于循环系统中，与年龄匹配的男性和绝经后女性相比，松弛素可能有助于绝经前女性所观察到的相对心血管保护作用。在本研究中，我们调查了松弛素对成年雌性和雄性小鼠以及怀孕期间动脉压正常调节的作用。通过无线电遥测技术测量了14周龄的雄性和雌性野生型（WT；C67BL/6xSv129）和松弛素基因敲除（KO）小鼠的平均动脉压（MAP）。此后，将雌性小鼠与相同基因型的（非遥测）雄性小鼠进行定时交配，并在整个妊娠期测量MAP。野生型雌性小鼠的基础MAP比雄性小鼠低约10 mmHg（<0.05）。松弛素缺乏会增加雌性小鼠的基础MAP（与野生型雌性小鼠相比，<0.05），但不会增加雄性小鼠的基础MAP。正如预期的那样，野生型小鼠在妊娠期MAP会降低。相反，在松弛素基因敲除小鼠中，妊娠中期和晚期动脉压会升高（与野生型相比，<0.05）。此外，松弛素缺乏会损害妊娠期体重增加并减少窝仔数。这是第一项（i）证明松弛素有助于小鼠动脉压的性别差异，以及（ii）记录怀孕的松弛素基因敲除小鼠动脉压变化情况的研究。了解绝经前女性动脉压调节的潜在机制可能会揭示治疗女性（非孕期和孕期）和男性高血压的新策略。
