Page hypertension as a model of pressure overload hypertrophy and diastolic dysfunction

Abstract

Patients with hypertension (HTN) are at risk for development of diastolic dysfunction (DD). Large animal models suitable for the study of the mechanisms accentuating HTN related DD are lacking. Our objective was to determine if experimental HTN produced by wrapping both kidneys in silk (“Page HTN”) was associated with DD and if this model is associated with neurohumoral activation at the systemic or local (cardiac) level. Weekly assessment of BP, plasma renin activity (PRA), angiotensin II (AII), endothelin (ET), brain natriuretic peptide (BNP), and norepinephrine (NEE) was performed for 5 weeks after wrapping both kidneys (HTN, n=7) or sham surgery (SHAM, n=6). LV function was assessed at 5 wks and tissue was harvested. Mean arterial pressure (MAP) was higher at 1 wk (p<0.05) in HTN vs SHAM groups and increased throughout the 5 wks in the HTN group. At 5 wks, MAP was 166±6 vs 124±4 mmHg in the HTN and SHAM groups (p<0.001). PRA, AII, ET, BNP and NEE were similar in the two groups prior to and at 1 wk after wrap or sham surgery. PRA was decreased from baseline at 5 wks in the HTN but not sham dogs. LV mass/body wt was higher in the HTN vs SHAM dogs (6.0±0.2 vs 4.9±0.3 g/Kg, p<0.01). At 5 wks systolic function and cardiac output were not different but arterial elastance was increased in the HTN vs SHAM groups. LV relaxation was slowed in the HTN group (p<0.05) but compliance was not different from the SHAM group. In the LV, BNP was increased but ET and AII were not different in the HTN vs SHAM groups. In summary, bilateral renal wrap produces HTN, hypertrophy and early DD without activation of circulating or local (cardiac) vasoconstrictor hormones. This model is easy to produce and may have similarities to patients with essential or renal HTN. This model will be useful for the study of HTN associated DD.