Departments of Oral Biology & Diagnostic Sciences, Augusta University, Augusta, Georgia, USA.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
Physiol Rep. 2023 Aug;11(15):e15771. doi: 10.14814/phy2.15771.
Nitric oxide (NO) contributes to blood pressure (BP) regulation via its vasodilatory and anti-inflammatory properties. We and others previously reported sex differences in BP in normotensive and hypertensive rat models where females have lower BP than age-matched males. As females are known to have greater NO bioavailability than age-matched males, the current study was designed to test the hypothesis that anesthetized female normotensive Wistar Kyoto rats (WKY) are more responsive to acute NOS inhibition-induced increases in BP compared to male WKY. Twelve-week-old male and female WKY were randomized to infusion of the nonspecific NOS inhibitor N -nitro-L-arginine methyl ester (L-NAME, 1 mg/kg/min) or selective NOS1 inhibition with vinyl-L-NIO (VNIO, 0.5 mg/kg/min) for 60 min. Mean arterial BP, glomerular filtration rate (GFR), urine volume, and electrolyte excretion were assessed before, and during L-NAME or VNIO infusion. L-NAME and VNIO significantly increased BP in both sexes; however, the increase in BP with L-NAME infusion was greater in females versus males compared to baseline BP values. Acute infusion of neither L-NAME nor VNIO for 60 min altered GFR in either sex. However, urine volume, sodium, chloride and potassium excretion levels increased comparably in male and female WKY with L-NAME and VNIO infusion. Our findings suggest sex differences in BP responses to acute non-isoform-specific NOS inhibition in WKY, with females being more responsive to L-NAME-induced elevations in BP relative to male WKY. However, sex differences in the BP response did not coincide with sex differences in renal hemodynamic responses to acute NOS inhibition.
一氧化氮（NO）通过其血管舒张和抗炎特性有助于血压（BP）调节。我们和其他人之前曾报道过在正常血压和高血压大鼠模型中，女性的血压低于同龄男性，存在血压的性别差异。由于女性的 NO 生物利用度大于同龄男性，因此本研究旨在测试以下假设：与同龄雄性 WKY 相比，麻醉的正常血压雌性 WKY 大鼠对急性 NOS 抑制诱导的血压升高更敏感。将 12 周龄的雄性和雌性 WKY 随机分为 N-硝基-L-精氨酸甲酯（L-NAME，1mg/kg/min）非特异性 NOS 抑制剂输注组或乙烯基-L-NIO（VNIO，0.5mg/kg/min）选择性 NOS1 抑制输注组，输注 60min。在输注 L-NAME 或 VNIO 之前和期间评估平均动脉压、肾小球滤过率（GFR）、尿量和电解质排泄。L-NAME 和 VNIO 均显著增加了两种性别的 BP；然而，与基线 BP 值相比，L-NAME 输注对雌性的 BP 升高作用大于雄性。急性输注 L-NAME 或 VNIO 60min 均未改变两性的 GFR。然而，与 L-NAME 和 VNIO 输注相比，雄性和雌性 WKY 的尿量、钠、氯和钾排泄水平均增加。我们的研究结果表明，WKY 对急性非同工型特异性 NOS 抑制的 BP 反应存在性别差异，与雄性 WKY 相比，雌性对 L-NAME 诱导的 BP 升高更敏感。然而，BP 反应的性别差异与急性 NOS 抑制对肾血流动力学反应的性别差异不相符。
