AT1A Receptors on Vasopressin‐Producing Cells are Important for Vasopressin Secretion but not Blood Pressure Responses to Chronic Intracerebroventricular Angiotensin in Mice

Abstract

Vasopressin (AVP) plays an important role in cardiometabolic physiology by elevating blood pressure and water reabsorption. This hormone is produced in the magnocellular neurosecretory cells (MNCs) within the supraoptic nucleus (SON) and periventricular nucleus (PVN) of the hypothalamus. Angiotensin II (ANG) has been shown to act at AT1A receptors in the brain and cause AVP‐dependent elevations in blood pressure. Critically, the contribution of AT1A receptors specifically on AVP‐producing cells to blood pressure remains unclear. We hypothesized that AT1A receptor knockout only from AVP‐expressing cells would prevent blood pressure elevations in response to chronic intracerebroventricular (ICV) ANG infusion. Mice with AT1A knockout from AVP‐producing cells (AT1AAVP‐KO) were generated by breeding AVP‐Cre mice with AT1Aflox mice. Subcutaneous osmotic mini‐pumps were used to infuse artificial cerebrospinal fluid (aCSF) or ANG (50 ng/hr) into the lateral cerebral ventricle. Blood pressure was measured daily by tail‐cuff plethysmography for three weeks before and two weeks following implantation surgery. Water intake and urine output were measured using metabolic cages. Baseline systolic blood pressure (SBP) was indistinguishable among groups (Control aCSF 113±2, Control ANG 112±2, AT1AAVP‐KO aCSF 114±3, AT1AAVP‐KO ANG 113±2 mmHg; p=ns). ANG increased SBP similarly in control and KO mice (Control aCSF 107±3, Control ANG 121±2, AT1AAVP‐KO aCSF 111±2, AT1AAVP‐KO ANG 119±4 mmHg; ANG p<0.05, genotype p=ns, interaction p=ns). Water intake (Control aCSF 2.8±0.3, Control ANG 13.3±3.3, AT1AAVP‐KO aCSF 2.2±0.3, AT1AAVP‐KO ANG 11.3±2.9 mL/day; ANG p<0.05, genotype p=ns, interaction p=ns) and urine output (Control aCSF 0.7±0.2, Control ANG 7.7±2.6, AT1AAVP‐KO aCSF 0.4±0.1, AT1AAVP‐KO ANG 6.4±1.9 mg/day; ANG p<0.05, genotype p=ns, interaction p=ns) were also increased by ANG but not different between genotypes. Interestingly, urine copeptin was elevated by ANG in controls but not AT1AAVP‐KO mice (Control aCSF 27.6±6.1, Control ANG 137.9±35.6, AT1AAVP‐KO aCSF 78.3±15.7, AT1AAVP‐KO ANG 60.0±15.7 mL/day; ANG p<0.05, genotype p=ns, interaction p<0.05). For all studies, Control aCSF n=14, Control ANG n=7, AT1AAVP‐KO aCSF n=14, AT1AAVP‐KO ANG n=10. These data support the conclusion that AT1A receptors on AVP‐expressing cells are important for the control of AVP secretion in response to ICV ANG, but that this specific sub‐population of receptors are of minor importance for SBP responses to ICV ANG.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.