Insights into the etiology of page hypertension - a model of hypertensive heart disease and diastolic dysfunction

Abstract

Background: Page (renal wrap) hypertension is an established model of experimental hypertension and produces hypertensive heart disease characterized by ventricular hypertrophy and fibrosis as well as diastolic dysfunction. Known vasoconstrictor systems (renin-angiotensin-aldosterone system, endothelin and catecholamines) are not activated in this model. The etiology of Page hypertension is unclear. We explored two possible mechanisms of hypertension in this model: one; role of sodium (Na) retention during the evolution of hypertension and two; production of a novel vasoconstrictor substance by the wrapped kidney. Methods: Two groups of mongrel dogs (sham, n = 6 and renal wrap, n = 6; age 1–2 years) were studied. 24-hour urine collections for Na were performed for one week before and four weeks after the wrap or sham surgery. The kidneys were harvested and extracts from cortex and medulla were tested for vasoconstrictor and vasodilatory properties in vitro using rat aortic strips in organ chamber experiments. Strips were pretreated with L-NMMA to control for any hemoglobin contamination of extracts. Seperate aortic strips were exposed to extracts after pre-constriction with norepinephrine to assess potential differential vasodilatory effects of extracts. Results: Blood pressure (see figure) in the renal wrapped animals was significantly higher than in the sham operated group. Renal function (serum creatinine), plasma renin activity and aldosterone levels were not significantlty different between the two groups (2-way ANOVA, p > 0.05). Urinary Na excretion over time was not significantly different between the two groups (see figure) (2-way ANOVA, p > 0.05). Both cortical and medullary renal extracts produced vasoconstriction in the aortic strips but there was no significant difference in the degree of vasoconstriction induced by extracts from wrapped or sham operated kidneys. While pre-constricted aortic strips showed relaxation with cortical extracts, medullary extracts produced further constriction. Again, the extent of constriction or relaxation produced by the renal tissue extracts was not significantly different between the sham operated and wrapped kidneys. Conclusions: Sodium retention does not contribute to evolution of hypertension following renal wrapping. No evidence exists for presence of novel active vasoconstrictor substance in wrapped kidneys. However, the renal production of a non-vasoactive precursor factor that is activated peripherally cannot be excluded. The etiology of Page hypertension remains unclear.