Further evidence against the role renal medullary perfusion in short-term control of arterial pressure in normotensive and mildly or overtly hypertensive rats

Bożena Bądzyńska,Janusz Sadowski,Iwona Baranowska

doi:10.1007/s00424-021-02534-1

Abstract

Earlier evidence from studies of rat hypertension models undermines the widespread view that the rate of renal medullary blood flow (MBF) is critical in control of arterial pressure (MAP). Here, we examined the role of MBF in rats that were normotensive, with modest short-lasting pressure elevation, or with overt established hypertension. The groups studied were anaesthetised Sprague-Dawley rats: (1) normotensive, (2) with acute i.v. norepinephrine-induced MAP elevation, and (3) with hypertension induced by unilateral nephrectomy followed by administration of deoxycorticosterone-acetate (DOCA) and 1% NaCl drinking fluid for 3 weeks. MBF was measured (laser-Doppler probe) and selectively increased using 4-h renal medullary infusion of bradykinin. MAP, renal excretion parameters and post-experiment medullary tissue osmolality and sodium concentration were determined. In the three experimental groups, baseline MAP was 117, 151 and 171 mmHg, respectively. Intramedullary bradykinin increased MBF by 45%, 65% and 70%, respectively, but this was not associated with a change in MAP. In normotensive rats a significant decrease in medullary tissue sodium was seen. The intramedullary bradykinin specifically increased renal excretion of water, sodium and total solutes in norepinephrine-treated rats but not in the two other groups. As previously shown in models of rat hypertension, in the normotensive rats and those with acute mild pressure elevation (resembling labile borderline human hypertension), 4-h renal medullary hyperperfusion failed to decrease MAP. Nor did it decrease in DOCA-salt model mimicking low-renin human hypertension. Evidently, within the 4-h observation, medullary perfusion was not a critical determinant of MAP in normotensive and hypertensive rats.

Highlights

Despite a substantial progress in the treatment of arterial hypertension over the past three decades, the effectiveness of the available therapeutic measures, including the novel approach based on catheter-based renal denervation [3, 30], is still limited and cannot be regarded as satisfactory
While in the past three decades the main effort in evaluation of the role of medullary blood flow (MBF) in control of BP focused on animal and human hypertension, the rate of medullary perfusion was proposed to be involved in the regulation of pressure fluctuations under physiological conditions [13, 22]
No evidence for a fall in BP despite an almost 50% increase in MBF maintained during four hours indicates that within this time interval medullary hyperperfusion has no role in control of BP in normotensive animals

Summary

Introduction

Despite a substantial progress in the treatment of arterial hypertension over the past three decades, the effectiveness of the available therapeutic measures, including the novel approach based on catheter-based renal denervation [3, 30], is still limited and cannot be regarded as satisfactory. The postulated crucial events in the mechanisms which correct elevation of BP include an increase in (allegedly poorly autoregulated) medullary blood flow (MBF) leading to increased renal interstitial hydrostatic pressure, first within the medulla and throughout the kidney (including the proximal peritubular space), followed by a change in Starling forces and inhibition of tubular transport and the development of natriuresis. In an earlier study with three variants of rat hypertension [11], we showed that experimental elevation of MBF had no rapid effect on BP, excluding thereby a possible role of medullary vasodilator (medullipin) allegedly released within less than 1 h after MBF elevation, as postulated by Muirhead [26]. We showed that longer lasting (4 h) medullary hyperperfusion failed to decrease BP in three models of rat hypertension [10]

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Conclusion