Mice lacking the ADP ribosyl cyclase CD38 exhibit attenuated renal vasoconstriction to angiotensin II, endothelin-1, and norepinephrine

Author:

Thai Tiffany L.,Arendshorst William J.

Abstract

ADP ribosyl (ADPR) cyclases comprise a family of ectoenzymes recently shown to influence cytosolic Ca2+concentration in a variety of cell types. At least two ADPR cyclase family members have been identified in mammals: CD38 and CD157. We recently found reduced renal vascular reactivity to angiotensin II (ANG II), endothelin-1 (ET-1), and norepinephrine (NE) in the presence of the broad ADPR cyclase inhibitor nicotinamide. We hypothesized that CD38 mediates effects attributed to ADPR cyclase. We found expression of ADPR cyclases CD38 and CD157 mRNA in spleen, thymus, skin, and preglomerular arterioles of wild-type (WT) animals. Mice lacking CD38 showed decreased CD157 expression in most tissues tested. No difference in systolic or mean arterial pressure was observed between strains in either conscious or anesthetized states, whereas heart rate was reduced 10–20% in CD38−/− animals ( P < 0.05). During anesthesia, CD38−/− mice had reduced basal renal blood flow (RBF) and urine excretion ( P < 0.05). RBF responses to intravenous injection of ANG II, ET-1, and NE were attenuated ∼50% in CD38−/− vs. WT mice ( P < 0.01 for all). The systemic pressor response to ANG II was decreased in the absence of CD38 ( P < 0.01), whereas that to NE was normal ( P > 0.05); ET-1 was administered at a nonpressor dose. Nicotinamide effectively inhibited ANG II-induced renal vasoconstriction in WT mice ( P < 0.001), but had no effect on renal responses to ANG II in CD38−/− mice ( P > 0.5). Overall, our observations indicate the presence of two ADPR cyclase family members in renal preglomerular resistance arterioles and the importance of CD38 participation in acute vascular responses to all three vasoconstrictors in the renal microcirculation.

Publisher

American Physiological Society

Subject

Physiology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3