Cardiac Hypertrophy and Vascular Dysfunction in Resistance Arteries Occurs Prior to the Onset of Hypertension in Schlager (BPH/2J) Mice

The Schlager inbred hypertensive (BPH/2J) mouse strain was developed by Gunther Schlager more than 45 years ago and have been recognized as a model of neurogenic hypertension. Activation of the sympathetic nervous system contributes to the maintainance of high blood pressure levels in BPH/2J male mice with the systolic blood pressure (SBP) starting to increase at seven weeks of age until reaching the highest value at 20 weeks of age. Several studies have shown cardiovascular dysfunction in these hypertensive mice, but no one has demonstrated whether heart and vascular dysfunction are present prior to the elevation in SBP. Our objective was to determine if cardiovascular dysfunction in male BPH/2J mice happens prior to the elevation of blood pressure. We hypothesized that cardiovascular remodeling along wih vascular dysfunction in mesenteric resistance arteries (MRA) occurs prior to the hypertension in BPH/2J mice, supporting the notion that the mechanism of hypertension in BPH/2J mice is not predominantly neurogenic. We evaluated intact-endothelium MRA function from 6-weeks-old male BPH/2J and normotensive control mice (BPN/3J). Intact-endothelium MRA were mounted on wire myographs. SBP was measured directly in the left carotid artery, and cardiac function and morphology was evaluated by echocardiography. Second harmonic generation was used to evaluate collagen deposition in MRA, and hematoxin and eosin staining done for cardiomyocyte hypertrophy. These data were analyzed using the Student t test ( p<0.05). SBP was not different between 6-weeks-old male BPH/2J and BPN/3J mice (78±2.33mmHg vs. 89±1.20 mmHg; n=3-4, respectively, p>0.05). BPH/2J presented increased left ventricle anterior wall thickness during systole (1.79±0.1mm) and diastole (1.13±0.06mm, n=4) compared to BPN/3J (systole: 1.46±0.08mm; diastole: 0.93±0.05mm, n=5, p<0.05). In addition, cardiomyocyte area values was higher in BPH/2J (1,188±51μm2, n=8) than BPN/3J (820±53μm2, n=4, p<0.05), suggesting that cardiac hypertrophy occurs prior to the onset of hypertension. BPH/2J mice presented increased phenylphrine-induced contraction (Rmax: BPH/2J: 6.25±0.54 vs. BPN/3J: 4.23±0.28 mN, n=4, p<0.05) and decreased endothelium-dependent relaxation (Rmax: BPH/2J: 76±5, n=4 vs. BPN/3J: 93±2%, n=3, p<0.05), and BPH/2J MRA presented a tendency to increase arterial collagen content compared to BPN/3J mice. These data reveal that cardiac remodeling and vascular dysfunction and fibrosis occurs prior to the elevation of SBP in BPH/2J mice, suggesting novel contributive causes of hypertension in Schlager mice. R00GM118885, R01HL149762, R00HL151889, and NHLBI (R00HL151889) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.