Jackson E K
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee.
J Pharmacol Exp Ther. 1989 Jul;250(1):9-21.
Sympathetic nerve stimulation causes a greater vascular response in spontaneously hypertensive rats (SHR) compared to Wistar-Kyoto normotensive rats (WKY), i.e., noradrenergic neurotransmission is enhanced in SHR. Prejunctional and/or postjunctional defects in the regulation of noradrenergic neurotransmission by endogenous prostaglandins could contribute to the increased responsiveness to sympathetic nerve stimulation in SHR. This hypothesis was tested by comparing the effects in SHR vs. WKY of inhibition of cyclooxygenase on vascular responses to periarterial nerve stimulation (PNS), norepinephrine (NE) and angiotensin II (ang II) in the in situ blood perfused rat mesentery. The cyclooxygenase inhibitor, indomethacin, potentiated vascular responses to PNS and NE similarly in 16-week old SHR vs. age-matched WKY. However, in this age group, indomethacin enhanced responses to ang II more in SHR compared with WKY. To determine whether chronic exposure of the vasculature to high blood pressure might alter the physiological significance of prostaglandin-mediated regulation of noradrenergic neurotransmission in vivo, additional studies were conducted in SHR and WKY that were 25 weeks old. In this age group, neither indomethacin nor ibuprofen, an alternative cyclooxygenase inhibitor, significantly potentiated responses to either PNS or NE in SHR, whereas in WKY both indomethacin and ibuprofen potentiated responses to PNS and NE. Also, in these older animals, indomethacin and ibuprofen enhanced responses to ang II equally in SHR vs. WKY. These findings indicate that in aging SHR prostaglandin-mediated regulation of vascular responses to sympathetic nerve stimulation becomes defective. This defect may contribute to the worsening of high blood pressure with age and may be involved in some of the vascular pathology associated with hypertension.
与Wistar-Kyoto正常血压大鼠（WKY）相比，交感神经刺激在自发性高血压大鼠（SHR）中引起更大的血管反应，即SHR中去甲肾上腺素能神经传递增强。内源性前列腺素对去甲肾上腺素能神经传递调节的节前和/或节后缺陷可能导致SHR对交感神经刺激的反应性增加。通过比较在原位血液灌注大鼠肠系膜中，环氧化酶抑制剂对SHR和WKY对动脉周围神经刺激（PNS）、去甲肾上腺素（NE）和血管紧张素II（ang II）的血管反应的影响，对这一假设进行了检验。环氧化酶抑制剂吲哚美辛在16周龄的SHR和年龄匹配的WKY中，对PNS和NE的血管反应增强作用相似。然而，在这个年龄组中，与WKY相比，吲哚美辛在SHR中对ang II的反应增强作用更大。为了确定血管长期暴露于高血压是否可能改变体内前列腺素介导的去甲肾上腺素能神经传递调节的生理意义，在25周龄的SHR和WKY中进行了额外的研究。在这个年龄组中，吲哚美辛和另一种环氧化酶抑制剂布洛芬在SHR中均未显著增强对PNS或NE的反应，而在WKY中，吲哚美辛和布洛芬均增强了对PNS和NE的反应。此外，在这些老年动物中，吲哚美辛和布洛芬在SHR和WKY中对ang II的反应增强作用相同。这些发现表明，在衰老的SHR中，前列腺素介导的对交感神经刺激的血管反应调节变得有缺陷。这种缺陷可能导致高血压随年龄增长而恶化，并可能参与一些与高血压相关的血管病理过程。
