engleski

Restored vascular relaxation in middle cerebral arteries (MCA) of renin-congenic rats

Renin congenic rats (RGRR) are derived by transferring part of chromosome 13 containing the renin gene from the Dahl R strain into the Dahl S genetic background. In contrast to Dahl S rats, RGRR exhibit normal regulation of the renin -angiotensin system (RAS) during changes in salt intake. The goal of this study was to determine whether responses to vasodilator stimuli that are lost in Dahl S rats are restored in RGRR rats showing normal regulation of the RAS. Responses to acetylcholine (ACh), hypoxia (PO2 reduction to 40-45 mm Hg), iloprost (stable PGI2 analog), cholera toxin (GS -protein activator) and DEA-NONOate (NO donor) were assessed in isolated MCA of male Dahl S and RGRR rats on low salt diet. MCA of Dahl S rats failed to dilate in response to ACh and exhibited paradoxical constriction to hypoxia and iloprost. Dilator responses to ACh and hypoxia (but not iloprost) were restored in RGRR. Dilation in response to cholera toxin and the NO donor were similar between strains. These results suggest that: 1) the prostacyclin signaling pathway is altered upstream of GS-protein in both strains of rats 2) vascular smooth muscle sensitivity to NO is preserved in Dahl S and RGRR and is not responsible for impaired relaxation in response to ACh in Dahl S rats, and 3) restoration of normal regulation of the RAS restores normal responses to ACh and hypoxia in RGRR congenic rats.

angiotensin; vascular relaxation; hypertension; microcirculation

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