Amiloride lowers arterial pressure in cyp1a1ren-2 transgenic rats without affecting renal vascular function.
OBJECTIVE
The epithelial sodium channel (ENaC) is expressed in the renal vasculature, where it may be involved in the control of vascular tone and arterial pressure. Using a rat model with an inducible mouse renin transgene (cyp1a1ren-2 transgenic rats), we tested the hypothesis that stimulation of the renin-angiotensin-aldosterone system (RAAS) for 3 weeks is associated with an impairment of renal vascular function that is sensitive to treatment with the ENaC blocker amiloride.


METHODS
Rats were randomized to control, transgene induction, or transgene induction plus amiloride treatment (n = 7-10 per group). Additional control animals were treated with amiloride. Arterial pressure was measured telemetrically. Sodium balance was determined in metabolic cages. Renal vascular function was investigated in vitro (wire myography) and in vivo (ultrasound flow probe). ENaC mRNA expression was determined by real-time PCR.


RESULTS
Transgene induction caused an increase in plasma aldosterone levels associated with a sustained elevation in arterial pressure. Amiloride elicited a transient decrease in renal sodium balance and effectively lowered arterial pressure. Neither transgene induction nor amiloride treatment significantly affected phenylephrine or acetylcholine-induced renal vascular responses. Similarly, small renal artery compliance and renal vascular resistance remained unaltered. Amiloride treatment caused an increase in α-ENaC mRNA abundance in renal cortical tissue but not in intrarenal arteries.


CONCLUSIONS
Amiloride reduces arterial pressure in cyp1a1ren-2 transgenic rats in association with increased renal sodium excretion without affecting renal vascular function. In this model of hypertension sustained activation of the RAAS does not lead to increased ENaC expression in small intrarenal arteries.
Schlüter
Torsten
T
Institute of Physiology, University of Greifswald, Karlsburg, Germany.
Rohsius
Robert
R
Wanka
Heike
H
Schmid
Catherina
C
Siepelmeyer
Anja
A
Rettig
Rainer
R
Peters
Jörg
J
Grisk
Olaf
O
D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D062686:Epithelial Sodium Channel Blockers; D051379:Mice; D009213:Myography / Q000379:methods; D019255:NADPH Oxidases / Q000378:metabolism; D051381:Rats; D055647:Rats, Transgenic; D012083:Renin / Q000235:genetics*; D012084:Renin-Angiotensin System; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012964:Sodium / Q000737:chemistry; D026941:Sodium Channel Blockers / Q000494:pharmacology; D019076:Transgenes
D062686:Epithelial Sodium Channel Blockers; D026941:Sodium Channel Blockers; D000584:Amiloride; D012964:Sodium; D019363:Cytochrome P-450 CYP1A1; D019255:NADPH Oxidases; D012083:Renin