Restoration of cerebral vascular relaxation in renin congenic rats by introgression of the Dahl R renin gene.
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.
Drenjancevic-Peric
Ines
I
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Weinberg
Brian D
BD
Greene
Andrew S
AS
Lombard
Julian H
JH
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D020296:Animals, Congenic; D004032:Diet; D018014:Gene Transfer Techniques; D020768:Middle Cerebral Artery / Q000187:drug effects* / Q000502:physiology; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology / Q000502:physiology; D051381:Rats; D020303:Rats, Inbred Dahl; D012083:Renin / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D055049:Salt Tolerance / Q000235:genetics; D014664:Vasodilation / Q000235:genetics*; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D009569:Nitric Oxide; D012083:Renin; D000109:Acetylcholine