Interaction of endothelin with renal nerves modulates kidney function in spontaneously hypertensive rats.
METHODS
We investigated kidney function, renal endothelin-1 concentration, prepro-endothelin-1 mRNA as well as endothelin receptor A and B mRNA expression and receptor properties in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) with intact renal nerves and 7 days after renal denervation. In addition, responses of renal function to the non-selective ETA/ETB receptor blocker bosentan (10 mg/kg i.v. bolus injection) were studied.


RESULTS
In SHR, renal papillary prepro-endothelin-1 mRNA expression, endothelin-1 tissue concentrations and endothelin receptor density were significantly lower than in normotensive rats. Renal denervation was associated with a decrease in papillary tissue prepro-endothelin-1 mRNA and in WKY rats also with a significant reduction in papillary endothelin-1 content without affecting ET receptor density. Bosentan did not alter renal blood flow or glomerular filtration rate but decreased urine flow rate in both intact normotensive and hypertensive rats, whereas it decreased urine sodium and potassium excretion only in intact WKY. Bosentan had no effects on renal function in renal denervated rats.


CONCLUSIONS
Since renal papillary endothelin-1 appears to counteract the fluid and sodium retaining effects of renal nerve activity, an impaired renal endothelin-1 synthesis in SHR may contribute to excessive sodium retention and thus to the pathogenesis of hypertension in SHR.
Girchev
Radoslav A
RA
Renal Section, Medical Policlinic, University of Bonn, Bonn, Germany. girchev@medfac.acad.bg
Bäcker
Angela
A
Markova
Petia P
PP
Kramer
Herbert J
HJ
D000818:Animals; D001794:Blood Pressure; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D007668:Kidney / Q000294:innervation* / Q000378:metabolism / Q000502:physiology*; D007672:Kidney Cortex / Q000378:metabolism; D007677:Kidney Function Tests; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017466:Receptors, Endothelin / Q000378:metabolism*
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D012333:RNA, Messenger; D017466:Receptors, Endothelin