Changes in mean arterial pressure predict degranulation of renomedullary interstitial cells

Abstract

1. Renomedullary interstitial cells (RMIC) are characterized by numerous intracellular granules thought to contain renal medullary antihypertensive substances. However, the nature of the trigger for RMIC degranulation remains to be elucidated. The present study examines the effects of acute alterations in mean arterial pressure (MAP) and medullary blood flow (MBF) on RMIC granulation. 2. Basal MAP and MBF in anaesthetized Sprague-Dawley rats (n = 4/group) were altered by intravenous infusions of vasoactive agents, including angiotensin II alone or with a nitric oxide (NO) synthase inhibitor (N-omega-nitro-l-arginine) or NO donor (sodium nitroprusside), noradrenaline and by carotid artery clamping. Following these treatments, kidneys were examined by electron microscopy and the absolute volume of granules in the renal medulla was calculated using unbiased stereological methods. 3. Acute increases in MAP, regardless of the treatment causing the increase, were associated with a reduction in the absolute volume of granules in the range of 42-67%. Regression analysis revealed that only increases in MAP, but not MBF, strongly predict RMIC degranulation. 4. Despite previous reports that changes in MBF activate renomedullary antihypertensive activity, we conclude that the change in MAP is an important determinant of the activity of the blood pressure-lowering mechanism of the renal medulla, with the assumption that the medullary lipids mediate the antihypertensive property of the renal medulla.

The effects of different inhibitory pathways of prostaglandin E2 biosynthesis on renomedullary interstitial cells in rats: a multidisciplinary study

“…The pro-hypertensive effect of kidney is regulated by locally active vasopressor systems, including renin-angiotensin system; while the anti-hypertensive effect is thought to depend on vasodepressor agents [1,13].…”

“…Tissue culture studies on RMICs revealed that these cells are specialized in PG synthesis [1,13]. It is well known that the most specific property of RMICs is the numerous lipid droplets they contain [1,3,8]. The number and size of these lipid droplets change according to the species and physiological state [1].…”

“…In 1969, Bohman and Maunsbach isolated lipid droplets from RMICs and found that they had a vasodepressor activity. The content of these lipid granules are believed to be storage units for precursors of prostaglandins (PGs), prostacyclin and medullipin [1]. The amount and the size of lipid droplets are shown to be involved in the changes of diuretic stages, water-salt balance, renal perfusion pressure (RPP) and medullary blood flow (MBF) [1].…”

“…The content of these lipid granules are believed to be storage units for precursors of prostaglandins (PGs), prostacyclin and medullipin [1]. The amount and the size of lipid droplets are shown to be involved in the changes of diuretic stages, water-salt balance, renal perfusion pressure (RPP) and medullary blood flow (MBF) [1]. RMICs are often arranged in rows between the loops of Henle and vasa recta, with their long axes being perpendicular to those of adjacent tubules and vessels, thus resembling the rungs of a ladder [3].…”

“…This anatomic arrangement suggests that RMICs may play an important role in maintaining urinary concentrating ability via preventing the axial diffusion in concentration gradient [5,6]. Studies demonstrate that the transplants of fragments from the renal medulla or of the cultured RMICs reverse renoprival hypertension [1,[7][8][9][10][11][12][13]. The biochemical analyses of these medullary transplants show the presence of prostaglandins (PGs), triglycerides, cholesterol esters and free fatty acids [14].…”