Reversal of Experimental Renovascular Hypertension Restores Coronary Microvascular Function and Architecture

Abstract

BACKGROUND Hypertension (HTN) may lead to left ventricular hypertrophy and vascular dysfunction, which are independent factors for adverse cardiovascular outcomes. We hypothesized that decreased blood pressure by percutaneous transluminal renal angioplasty (PTRA) would improve the function and architecture of coronary microvessels, in association with decreased inflammation and fibrosis. METHODS Three groups of pigs were studied: normal, HTN, and HTN+PTRA. After 6 weeks of renovascular HTN, induced by placing a local-irritant coil in the renal artery, pigs underwent PTRA or sham. Four weeks later multidetector-computed tomography (CT) was used to assess systolic, diastolic, and microvascular function, and responses to adenosine. Microvascular architecture, oxygen sensors, inflammation, and fibrosis were then explored in cardiac tissue. RESULTS PTRA successfully decreased blood pressure and left ventricular hypertrophy. Basal fractional vascular volume (FVV) was similar among the groups, but its response to adenosine was significantly attenuated in HTN, whereas microvascular permeability (MP) and response to adenosine were greater than normal. Both were restored by PTRA. These were accompanied by increased myocardial expression of hypoxia-inducible factor (HIF)-1α, inflammation, and microvascular remodeling, including increased density of epicardial microvessels (20–200 µm), as well as cardiac diastolic dysfunction, all of which improved by reversal of HTN. However, PTRA only partially decreased myocardial fibrosis. CONCLUSIONS Reversal of early renovascular HTN improved coronary microvascular function and architecture and reversed myocardial hypertrophy and diastolic dysfunction, in association with decreased levels of myocardial ischemia and inflammation markers, underscoring the benefits of blood pressure normalization for preservation of cardiovascular function and structure.

Mitochondrial targeted peptides attenuate residual myocardial damage after reversal of experimental renovascular hypertension

“…We have previously shown in a swine model of nonatherosclerotic RAS that revascularization successfully decreases blood pressure, improves coronary microvascular architecture, and reverses myocardial hypertrophy and diastolic dysfunction [30]. However, simulation of the clinical scenario by superimposition of atherosclerosis aggravates myocardial microvascular dysfunction and oxidative stress in experimental RVHT [31].…”

T1 mapping in cardiac MRI

“…However, increased capillary density or vasodilatation would also increase ECV, although to a smaller extent [48]. Therefore, ECV changes in isolation require interpretation.…”

Regression of Coronary Microvascular Changes: The Role of Blood Pressure-Lowering Treatment

“…Despite its high scientific quality, the study by UrbietaCaceres et al 5 has a number of limitations, mostly noted by the authors. First, the rather small sample size (six to seven animals in each group) might have introduced bias.…”

“…Second, microvascular changes were assessed after 10 weeks of renovascular hypertension. A longer duration of hypertension, as commonly found in human hypertension, might induce Although investigation on the effect of antihypertensive treatment on structural coronary microvascular changes has been generally hampered by the lack of objective and reproducible methods of investigation, the approach used by Urbieta-Caceres et al 5 represents a step toward a more comprehensive understanding of the effects of antihypertensive treatment on coronary microcirculation, and indicates new potential additional targets of blood pressure-lowering treatment. Their findings are provocative enough to be explored further in larger studies.…”

“…In this issue of the Journal, Urbieta-Caceres et al 5 aimed to investigate whether reversal of experimental renovascular hypertension would improve the function and architecture of coronary microvessels, in association with decreased left ventricular mass, inflammation, and fibrosis. Three groups of domestic pigs were examined, one with renovascular hypertension induced by an irritant coil placed in the renal artery, one with renovascular hypertension successfully treated after 6 weeks with renal angioplasty and stenting, and a normal control group.…”