Pressure independence of renin release by isolated kidneys of Lyon hypertensive rats.

Abstract

In the present work the influence of perfuslon pressure on renal functions and renin release was studied before and after the blockade of thromboxane A 2 /prostaglandin H 2 (TXA 2 /PGH 2 ) receptors using isolated kidneys from 7-week-old genetically hypertensive (LH), nonnotensive (LN), and low blood pressure (LL) rats of the Lyon strain. Kidneys were single pass perfused with Krebs-Henseleit solution with a gelatine derivative (Polygeline) added as an oncotic agent A servocontrolled system stabilized the renal perfusion pressure (RPP) at any chosen (±1 mm Hg) level. In baseline conditions (RPP, 90 mm Hg), LH (n=7) kidneys differed from LN (n=6) and LL (n=8) controls by increased vascular resistance, decreased glomerular filtration rate, and natriuresis. The LH kidney responses to stepwise changes in RPP (between 60 and 170 mm Hg) differed from those of LN and LL rats by a significantly lower perfusion flow, glomerular filtration rate, and natriuresis. Above all, the reduction in RPP, which induced a marked and highly reproducible renin release in LN and LL kidneys, was devoid of effects in LH kidneys. The blockade of TXAJ/PGHJ receptors by AH23848 (4x 10~' M) did not change the baseline (RPP, 90 mm Hg) functions of kidneys of the three strains. During changes in RPP, the responses of LN and LL kidneys were not modified, whereas LH kidneys exhibited significant increases in both glomerular filtration rate and natriuresis. Finally, AH23848 significantly decreased the renin release by kidneys of the three strains. It is concluded that renin release of LH isolated kidneys is independent of the perfusion pressure and that renal TXA 2 /PGH 2 receptor activation participates in the renin release and in the altered functions exhibited by kidneys of LH rats. Several recent experiments using kidney transplantation 12 have emphasized the primary role played by the kidney in the pathogenesis of genetic hypertension. Obviously, among the pressor factors originating in the kidney, the most important is the renin-angiotensin system. In Lyon genetically hypertensive (LH) rats, the plasma renin activity is normal in young animals and low in adult ones. 3 Similar findings have been reported in Japanese spontaneously hypertensive rats (SHR). 4 Despite these low levels of plasma renin, both models are highly sensitive to the blockade of the renin-angiotensin system. 5 -6 This demonstrates that, in genetically hypertensive rats, the low renin levels remain inappropriate and actively contribute to blood pressure elevation.Such an inappropriate renin secretion may reflect a polymorphism of the renin gene, as found in Dahl saJt-sensitive rats, 7 or an abnormal control by its physiological regulators. Because the renin gene polymorphism in LH rats does not appear directly related to the blood pressure level, 8 we thought it of interest to assessFrom the Department of Physiology and Clinical Pharmacology,

Renal effects of cP450 arachidonate metabolites in the Lyon hypertensive rat

“…Finally, our results confirm those obtained by Medeiros et al [9] showing that the renin release by LH kidneys is markedly reduced and largely independent of the RPP. In addition, they demonstrate that 7-ER decreased the renin release at low RPP in LN kidneys.…”

Acute pressure–natriuresis function shows early impairment in Lyon hypertensive rats

“…Although the activity of renin-angiotensin system was not controlled, it is unlikely that the pressure-dependent renin release markedly contributed to the alteration of pressure natriuresis in LH rats. Indeed, in this strain, the renin release is stimulated when RPP is lowered below the threshold pressure of about 70-80 mmHg; over this threshold pressure, renin is poorly responsive to changes in RPP [11,12]. In addition, we previously observed that the differences in pressure natriuresis between LH and LL rats persisted even when rats received early (from 3 weeks of age) and chronic treatment with an angiotensin-converting enzyme inhibitor [7].…”

Elevated Epidermal Growth Factor Receptor Levels in Hypertensive Lyon Rat Kidney and Aorta

“…In this regard, it is noteworthy that it has recently been demonstrated that renin release is independent of perfusion pressure in the isolated kidneys of LH rats, suggesting that the hypertension in LH rats may be interpreted as associated with a relative excess of angiotensin. 22 The increase in EGFR numbers in adult animals may be a cause or consequence of the increasing BP. In a separate tissue EGFR mRNA levels of SHR and control normotensive rats were analysed after a period of 8 weeks of hydralazine treatment.…”