Activation of the humoral antihypertensive system of the kidney increases diuresis.

Abstract

SUMMARY Isolated kidneys taken from normotensive Wistar-Kyoto rats were cross-perfused extracorporeally by normotensive strain-matched donor rats. The extracorporeal perfusion circuit was arranged so that the perfusion pressure to the normotensive recipient kidney could be varied from 90 to 200 mm Hg without any change in total flow through this circuit. This setup avoided hemodynamic or mechanical interferences with reflexogenic circulatory control in the normotensive donor rat when the recipient kidney was manipulated. Diuresis and natriuresis were measured in the normotensive donor rat and the normotensive recipient kidney. A few minutes after normotensive recipient kidney perfusion pressure had been raised, mean arterial pressure (MAP) and heart rate started to decline rapidly in the normotensive donor rat, and circulatory collapse ensued within 15 to 100 minutes. During the control period at 90 mm Hg normotensive recipient kidney perfusion pressure, urinary flow, MAP and heart rate were stable in the normotensive donor rat and the normotensive recipient kidney. When perfusion pressure was raised to 200 mm Hg in the recipient kidney, the urinary flow in the donor rat increased 62% on average in the first 10 minutes over values recorded before the pressure rise (p<0.05) while MAP simultaneously fell by 16% and HR remained unchanged. During the subsequent period, the urinary flow of the donor rat declined together with MAP and heart rate. In the extracorporeally high-pressure perfused recipient kidneys, an eightfold to ninefold increase in diuresis and natriuresis occurred during the first 45 minutes. In conclusion, the present study lends further support to the theory that the humoral renal antihypertensive system is involved in ordinary blood pressure regulation and in the control of kidney excretory function as a possible counterpart to the renocortical renin-angiotensin system. (Hypertension 11: 597-601,1988) KEY WORDS • rats • renomedullary antihypertensive system • Wistar-Kyoto rats diuresis • natriuresis • kidney function • perfusion • renomedullary lipids * pressure-related natriuresis D URING the last decade, results have accumulated showing that the medulla of the kidney harbors an important humoral antihypertensive mechanism that also may be involved in normal blood pressure regulation.1 " 3 Many positive feedback loops have been identified in primary (essential) hypertension that tend to increase pressure, 4 and when combined, they would seem capable of raising blood From the

Evidence for a renomedullary vasodepressor system in rabbits and dogs.

“…- 11 Karlstrom et al 3 suggested that the renal medullary system is natriuretic and some of the data from the present study supports this. The natriuresis was significantly less in BEA-treated rabbits than in untreated rabbits even though renal perfusion pressure was similar, but this may be explained by altered fluid balance status in these rabbits.…”

“…Swales and colleagues 2 then showed that destruction of the renal medulla retarded the fall in blood pressure after the removal of a renal artery clip from Goldblatt hypertensive rats. The possibility that increased renal perfusion may release one or more medullary depressor hormones received strong support recently from Karlstrom and colleagues, 3 who demonstrated that increasing the perfusion pressure of isolated kidneys released a depressor substance in the venous effluent that when infused into conscious rats, produced profound hypotension.…”

“…We have now studied whether evidence for renal medullary vasodepressor hormones can be found in other mammalian species, namely, rabbits and dogs. The experiments use an approach similar to that of Karlstrom and colleagues, 3 but allow alteration of renal perfusion pressure in situ. In rabbits, we studied whether increased renal perfusion pressure caused systemic hypotension and whether chemical renal medullectomy abolished this response.…”

Interactions Between Furosemide and the Renal Sympathetic Nerves

“…Since prostaglandin-mediated vasodilation is endothelium-independent, Gerkens and coworked formed the hypothesis that furosemide stimulates renal prostaglandin synthesis which in turn causes release of a renomedullary antihypertensive hormone to the circulation (Gerkens 1987). The final renomedullary hormone is not yet defined, but circumstantial evidence suggest that a renomedullary lipid (medullipin I) is released from the renal medulla in response to increased renal perfusion pressure, and that the active hepatic metabolite (medullipin 11) has vasodilatory, sympathoinhibitory, and diuretic-natriuretic actions (Muirhead et al 1983;Karlstrom et al 1988Karlstrom et al & 1989Christy et al 1993;Thomas et al 1994). Whether renomedullary lipids have actions on capacitance vessels and the pulmonary circulation is unknown.…”

The role of nephrectomy and proadifen in blood pressure homeostasis following an acute kinin‐induced hypotension in normotensive rats

“…Medullipin I is conveyed to the liver where it is converted to the active vasodilator compound, medullipin II, by the cytochrome P-450 enzyme system (Muirhead et al, 1989b). Furthermore, renal medullipin I-secretion is increased when renal perfusion pressure is increased (Karlstr6m & Gothberg, 1987;Karlstrom et al, 1988). Thus, activation of 'Author for correspondence.…”