Renal vascular dysfunction precedes the development of renal damage in the hypertensive Fawn-Hooded rat

Abstract

It is unknown whether generalized vascular dysfunction precedes the development of kidney disease. Therefore, we studied myogenic constriction and endothelium-mediated dilatory responses in two inbred Fawn-Hooded (FH) rat strains, one of which spontaneously develops hypertension, proteinuria, and glomerulosclerosis (FHH), whereas the other (FHL) does not. Small renal, mesenteric resistance arteries and thoracic aorta isolated from FH rats before (7 wk old) and after the development of mild proteinuria (12 wks old) were mounted in perfused and isometric set-ups, respectively. Myogenic response, endothelium-dependent relaxation, and the contribution of endothelium-mediated dilatory compounds were studied using their respective inhibitors. Myogenic reactivity was assessed constructing pressure-diameter curves in the presence and absence of calcium. At the age of 7 wk, renal arteries isolated from kidneys of FHH rats developed significantly lower myogenic tone compared with FHL, most likely because of excessive cyclo-oxygenase 1-mediated production of constrictive prostaglandins. Consequently, young FHH demonstrated reduced maximal myogenic tone (22 +/- 4.8 vs. 10.8 +/- 2.0%, P = 0.03) and the peak myogenic index (-6.9 +/- 4.8 vs. 0.6 +/- 0.8%/mmHg, P = 0.07 for FHL vs. FHH, respectively). Active myogenic curves obtained in mesenteric arteries isolated from 7-wk-old rats did not differ between either strain, demonstrating a similar level of systemic myogenic tone in FHL and FHH rats. Therefore, before any renal end-organ damage is present, myogenic response seems selectively impaired in renal vasculature of FHH rats. Aortic reactivity did not differ between FHL and FHH at the time points studied. The present study shows that vascular dysfunction in both small renal and systemic arteries precedes renal end-organ damage in a spontaneous model of hypertension-associated renal damage. These early vascular changes might be potentially involved in the increased susceptibility of FHH rats to renal injury.

Development of the Renal Arterioles

“…61 It is unknown what mechanisms establish phenotypic variability in the vascular beds and how these might function for the maintenance of a healthy vascular system. When formation of the kidney vasculature is altered, the consequences are devastating, as exemplified by the serious developmental defects described above, occurring in animals and humans with ablation of renin cell precursors, mutations of the renin-angiotensin system, and a lack of miRNAs in the renal vasculature, resulting in early arterial and arteriolar abnormalities that are followed by the deterioration of kidney structure and function.…”

Renal myogenic constriction protects the kidney from age-related hypertensive renal damage in the Fawn-Hooded rat

“…Renal interlobar arteries of the fawn-hooded hypertensive (FHH) rat exhibit a diminished myogenic constriction already at young age, preceding renal impairment and hypertension. Along with elevation of blood pressure in the FHH rat, renal damage starts to develop [11]. Taken together, these data suggest that preservation of vascular myogenic function of renal vessels in hypertension might be of prime importance to shield the kidney from glomerular changes and ultimately, CRF.…”

Vascular smooth muscle function of renal glomerular and interlobar arteries predicts renal damage in rats

“…This view is substantiated by observations in animal models of renal failure (fawn-hooded hypertensive rat), in which a loss of MC in interlobar arteries precedes renal damage which develops only when systemic blood pressure increases (12). In contrast, spontaneously hypertensive rats (SHR), who have high systemic blood pressure, do not show renal damage.…”