Faculty Collaboration Database

Restoration of cerebral vascular relaxation in renin congenic rats by introgression of the Dahl R renin gene. Am J Hypertens 2010 Mar;23(3):243-8

Date

12/05/2009

Pubmed ID

19959997

Pubmed Central ID

PMC2924749

DOI

10.1038/ajh.2009.236

Scopus ID

2-s2.0-76749161854 (requires institutional sign-in at Scopus site)   11 Citations

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 (PO2 reduction to 40-45 mm Hg), 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.

Author List

Drenjancevic-Peric I, Weinberg BD, Greene AS, Lombard JH

MESH terms used to index this publication - Major topics in bold

Acetylcholine
Animals
Animals, Congenic
Diet
Gene Transfer Techniques
Middle Cerebral Artery
Models, Animal
Muscle, Smooth, Vascular
Nitric Oxide
Rats
Rats, Inbred Dahl
Renin
Renin-Angiotensin System
Vasodilation
Vasodilator Agents