Academic Journal
Knockout of Macula Densa Neuronal Nitric Oxide Synthase Increases Blood Pressure in db/db Mice
| العنوان: | Knockout of Macula Densa Neuronal Nitric Oxide Synthase Increases Blood Pressure in db/db Mice |
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| المؤلفون: | Zhang, Jie, Wang, Ximing, Cui, Yu, Jiang, Shan, Wei, Jin, Chan, Jenna, Thalakola, Anish, Le, Thanh, Xu, Lan, Zhao, Liang, Wang, Lei, Jiang, Kun, Cheng, Feng, Patel, Trushar, Buggs, Jacentha, Vallon, Volker, Liu, Ruisheng |
| المصدر: | Hypertension ; volume 78, issue 6, page 1760-1770 ; ISSN 0194-911X 1524-4563 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health) |
| سنة النشر: | 2021 |
| الوصف: | Hypertension is a common comorbid condition in patients with diabetes. The pathogenesis of hypertension in diabetes has not been fully clarified. Primary tubular hyperreabsorption may contribute, which may be counteracted by glomerular hyperfiltration in the early diabetic kidney. In this study, we hypothesize that in early diabetes, the macula densa neuronal nitric oxide synthase (NOS1)-derived nitric oxide (NO) production is enhanced, which blunts tubuloglomerular feedback (TGF) response, promotes glomerular hyperfiltration, and maintains normal blood pressure; conversely, insufficient NO generation by the macula densa induces hypertension by lowering glomerular filtration rate and thus inhibiting natriuresis. To test this hypothesis, we examined the changes of macula densa NOS1 expression and phosphorylation as well as NO production, TGF response, glomerular filtration rate, sodium excretion, and blood pressure in a murine model of leptin receptor-deficient (db/db) diabetes with or without macula densa-specific NOS1 deletion. We found that db/db mice presented reduced fractional renal sodium excretion and only a small increase in blood pressure, associated with upregulated expression and activity of macula densa NOS1, inhibited TGF response, and glomerular hyperfiltration. Genetic knockout of macula densa NOS1 restored the TGF response and attenuated glomerular hyperfiltration in db/db mice but also further reduced fractional renal sodium excretion and substantially increased blood pressure. In conclusion, the present study demonstrates that in the early stage of leptin receptor-deficient diabetes, the upregulation of macula densa NOS1 inhibits TGF and increases glomerular filtration rate, which counteracts renal sodium retention and limits the rise in blood pressure. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1161/hypertensionaha.121.17643 |
| DOI: | 10.1161/HYPERTENSIONAHA.121.17643 |
| الاتاحة: | http://dx.doi.org/10.1161/hypertensionaha.121.17643 https://www.ahajournals.org/doi/full/10.1161/HYPERTENSIONAHA.121.17643 |
| رقم الانضمام: | edsbas.AEB1398B |
| قاعدة البيانات: | BASE |
| DOI: | 10.1161/hypertensionaha.121.17643 |
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