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In the present study, we hypothesized that the effect of ANG II on the macula densa nitric oxide (NO) synthase 1\u03b2 (NOS1\u03b2)-mediated tubuloglomerular feedback (TGF) mechanism is different between males and females, thereby contributing to the sexual dimorphism of ANG II-induced hypertension. We used microperfusion, micropuncture, clearance of FITC-inulin, and radio telemetry to examine the sex differences in the changes of macula densa NOS1\u03b2 expression and activity, TGF response, natriuresis, and blood pressure (BP) after a 2-wk ANG II infusion in wild-type and macula densa-specific NOS1 knockout mice. In wild-type mice, ANG II induced higher expression of macula densa NOS1\u03b2, greater NO generation by the macula densa, and a lower TGF response in vitro and in vivo in females than in males; the increases of glomerular filtration rate, urine flow rate, and Na<jats:sup>+<\/jats:sup> excretion in response to an acute volume expansion were significantly greater and the BP responses to ANG II were significantly less in females than in males. In contrast, these sex differences in the effects of ANG II on TGF, natriuretic response, and BP were largely diminished in knockout mice. In addition, tissue culture of human kidney biopsies (renal cortex) with ANG II resulted in a greater increase in NOS1\u03b2 expression in females than in males. In conclusion, macula densa NOS1\u03b2-mediated TGF is a novel and important mechanism for the sex differences in ANG II-induced hypertension. <\/jats:p>","DOI":"10.1152\/ajprenal.00312.2020","type":"journal-article","created":{"date-parts":[[2020,10,12]],"date-time":"2020-10-12T18:56:45Z","timestamp":1602529005000},"page":"F908-F919","source":"Crossref","is-referenced-by-count":10,"title":["A new mechanism for the sex differences in angiotensin II-induced hypertension: the role of macula densa NOS1\u03b2-mediated tubuloglomerular feedback"],"prefix":"10.1152","volume":"319","author":[{"given":"Jie","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Public Health, University of South Florida, Tampa, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Science, College of Pharmacy, University of South Florida, Tampa, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology, H. 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