Restoration of cerebral vascular relaxation in renin congenic rats by introgression of the dahl R renin gene

Abstract

Background: This study determined whether transfer of the renin gene from the Dahl salt-resistant (Dahl R) strain into the Dahl salt-sensitive (SS) genetic Background: restores the relaxation of middle cerebral arteries (MCAs) to different vasodilator stimuli in S/renRR renin congenic (SS.SR-(D13N1 and Syt2)/Mcwi) (RGRR) rats maintained on low-salt (0.4% NaCl) diet. Methods: Responses to vasodilator stimuli were evaluated in isolated MCA from SS (Dahl SS/Jr/Hsd/MCWi), RGRR rats, and Dahl R rats. Results: MCA from SS rats failed to dilate in response to acetylcholine (ACh; 10 6 mol/l), hypoxia (PO 2 reduction to 40-45mmHg), and iloprost (10 11 g/ml). ACh-and hypoxia-induced dilations were present in Dahl R rats and restored in RGRR rats. MCA from RGRR and SS constricted in response to iloprost, whereas MCA from Dahl R rats dilated in response to iloprost. MCA from SS, RGRR, and Dahl R rats exhibited similar dilations in response to cholera toxin (10 9 g/ml) and dialated in response to the nitric oxide (NO) donor DEA-NONOate (10 5 mol/l). Conclusions: (i) Restoration of normal regulation of the renin-angiotensin system restores dilations to ACh and hypoxia that are impaired in SS rats, (ii) prostacyclin signaling is impaired in SS and RGRR rats but intact in Dahl R rats, indicating that alleles other than the renin gene affect vascular relaxation in response to this agonist; and (iii) vascular smooth muscle sensitivity to NO is preserved in SS and RGRR and is not responsible for impaired arterial relaxation in response to ACh in SS rats. © 2010 American Journal of Hypertension, Ltd.