Naslov
Normal regulation of renin-angiotensin system (RAS) restores vasodilator mechanisms in middle cerebral arteries (MCA) of consomic SS.BN13 and renin-congenic rats

Autori
Drenjančević-Perić Ines ; Lombard, JH.

Izvornik
FASEB Journal (0892-6638) 18 (2004), 4; A248-A249

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, kongresno priopcenje, znanstveni

Ključne riječi
angiotensin II; hypertension; consomic and congenic rats; vascular reactivity

Sažetak
Dahl S rats exhibit impaired regulation of the RAS with chronic low levels of angiotensin II (ANG II) while consomic SS.BN13 rats and renin-congenic (RGRR) rats with a normally functioning renin gene from the Brown Norway (BN) or Dahl salt-resistant rat exhibit normal RAS regulation. Since ANG II plays a role in maintaining normal vascular relaxation mechanisms, the goal of this study was to determine whether restoring normal RAS regulation by chromosome/gene transfer affects relaxation of MCA from rats on a low salt diet. Responses to acetylcholine (ACh) and hypoxia were assessed by videomicrometry in cannulated MCA in the absence and /or presence of indomethacin [cyclooxygenase (COX) inhibitor], L-NMMA (NOS inhibitor), and MS-PPOH (CYP450 epoxygenase inhibitor). MCA from Dahl S rats exhibited paradoxical constriction in response to acetylcholine (ACh) that was eliminated by COX inhibition, while ACh-induced dilation was completely NO dependent in BN, SS.BN13 and RGRR rats. Hypoxic constriction of MCA from Dahl S rats was converted to dilation by indomethacin. The restored dilation was unaffected by L-NMMA, but abolished with MS-PPOH suggesting a role for EETs. In SS.BN13, RGRR, and BN rats, hypoxic dilation was eliminated by indomethacin, suggesting a role for some COX metabolite, e.g., prostacyclin or PGE2. These data suggest that normalization of RAS regulation causes a switch from production of COX derived vasoconstrictor metabolites (in Dahl S rats) toward NO-dependent relaxation in response to ACh and prostaglandin-dependent dilation to hypoxia.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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