التفاصيل البيبلوغرافية
| العنوان: |
Long-term blood pressure lowering and cGMP-activating actions of the novel ANP analog MANP. |
| المؤلفون: |
Yang Chen, Schaefer, Jacob J., Iyer, Seethalakshmi R., Harders, Gerald E., Shuchong Pan, Sangaralingham, S. Jeson, Chen, Horng H., Redfield, Margaret M., Burnett Jr., John C. |
| المصدر: |
American Journal of Physiology: Regulatory, Integrative & Comparative Physiology; Apr2020, Vol. 318 Issue 4, pR669-R676, 8p |
| مصطلحات موضوعية: |
BLOOD pressure, GUANYLATE cyclase, SMOOTH muscle, SUBCUTANEOUS injections, MUSCLE cells |
| مستخلص: |
Based on the cardiac hormone atrial natriuretic peptide (ANP) and its seminal role in blood pressure (BP) homeostasis, we investigated the chronic BP lowering actions of a novel ANP analog currently entering clinical trials for hypertension. Previous reports demonstrate that this analog MANP activates the guanylyl cyclase A receptor (GC-A) and results in more potent biological actions compared with ANP; thus, it may represent a new therapeutic drug for hypertension. A major goal of this study was to establish that chronic subcutaneous delivery of MANP is feasible and hypotensive together with cGMP effects. We investigated the BP-lowering and cGMP-activating actions of acute and chronic subcutaneous delivery in normal and hypertensive rats. Furthermore, we explored vascular mechanisms of MANP in human aortic smooth muscle cells (HASMC) and ex vivo in isolated arteries. In normal rats with a single subcutaneous injection, MANP promoted robust dose-dependent BPlowering actions and natriuresis, together with cGMP activation. Most importantly in hypertensive rats, once-a-day subcutaneous injection of MANP for 7 days induced cGMP elevation and long-term BP reduction compared with vehicle. Mechanistically, in HASMC, MANP activated cGMP and attenuated angiotensin II-mediated increases in intracellular Ca2+ levels while directly vasorelaxing arterial rings. Our study demonstrates for the first time the effectiveness of subcutaneous administration of MANP for 7 days and provides innovative, vascular mechanisms of BP regulation supporting its continued development as a novel therapeutic for hypertension. [ABSTRACT FROM AUTHOR] |
|
Copyright of American Journal of Physiology: Regulatory, Integrative & Comparative Physiology is the property of American Physiological Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
