Sex Differences in the Pressor and Tubuloglomerular Feedback Response to Angiotensin II
- 1 January 2012
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Hypertension
- Vol. 59 (1), 129-135
- https://doi.org/10.1161/hypertensionaha.111.178715
Abstract
Awareness of sex differences in the pathology of cardiovascular disease is increasing. Previously, we have shown a role for the angiotensin type 2 receptor (AT 2 R) in the sex differences in the arterial pressure response to Ang II. Tubuloglomerular feedback (TGF) contributes in setting pressure-natriuresis properties, and its responsiveness is closely coupled to renal Ang II levels. We hypothesize that, in females, the attenuated pressor response to Ang II is mediated via an enhanced AT 2 R mechanism that, in part, offsets Ang II–induced sensitization of the TGF mechanism. Mean arterial pressure was measured via telemetry in male and female wild-type (WT) and AT 2 R knockout (AT 2 R-KO) mice receiving Ang II (600 ng/kg per minute SC). Basal 24-hour mean arterial pressure did not differ among the 4 groups. After 10 days of Ang II infusion, mean arterial pressure increased in the male WT (28±6 mm Hg), male AT 2 R-KO (26±2 mm Hg), and female AT 2 R-KO (26±4 mm Hg) mice, however, the response was attenuated in female WT mice (12±4 mm Hg; P between sex and genotype=0.016). TGF characteristics were determined before and during acute subpressor Ang II infusion (100 ng/kg per minute IV). Basal TGF responses did not differ between groups. The expected increase in maximal change in stop-flow pressure and enhancement of TGF sensitivity in response to Ang II was observed in the male WT, male AT 2 R-KO, and female AT 2 R-KO but not in the female WT mice ( P between sex and genotype 2 R-mediated pathway counterbalances the hypertensive effects of Ang II and attenuates the Ang II–dependent resetting of TGF activity in females. Thus, the enhancement of the AT 2 R may, in part, underlie the protection that premenopausal women demonstrate against cardiovascular disease.Keywords
This publication has 37 references indexed in Scilit:
- Gender Differences in Pressure-Natriuresis and Renal AutoregulationHypertension, 2011
- Sex differences in acute ANG II-mediated hemodynamic responses in miceAmerican Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2010
- Protective actions of estrogen on angiotensin II-induced hypertension: role of central nitric oxideAmerican Journal of Physiology-Heart and Circulatory Physiology, 2009
- Enhanced Angiotensin II Type 2 Receptor Mechanisms Mediate Decreases in Arterial Pressure Attributable to Chronic Low-Dose Angiotensin II in Female RatsHypertension, 2008
- AT2 receptors: Functional relevance in cardiovascular diseasePharmacology & Therapeutics, 2008
- Role of Extracellular Superoxide Dismutase in the Mouse Angiotensin Slow Pressor ResponseHypertension, 2006
- Sexual dimorphism in angiotensin II-induced hypertension and vascular alterationsCanadian Journal of Physiology and Pharmacology, 2005
- Sex and the Renin Angiotensin System: Implications for Gender Differences in the Progression of Kidney DiseaseAdvances in Renal Replacement Therapy, 2003
- Gender Differences in Development of Hypertension in Spontaneously Hypertensive RatsHypertension, 2000
- Impact of gender on the renal response to angiotensin IIKidney International, 1999