Restoration of normal vascular relaxation mechanisms in cerebral arteries by chromosomal substitution in consomic SS.13BN rats.
This study sought to identify the mechanisms of vascular relaxation that are rescued in middle cerebral arteries (MCA) of SS.13BN consomic rats by substituting chromosome 13 containing the renin gene from Brown Norway (BN) rats into the Dahl salt-sensitive (SS) genetic background. Isolated MCA from SS rats exhibited an indomethacin-sensitive constriction in response to acetylcholine (ACh) and hypoxia. ACh-induced dilation was NO dependent and hypoxic dilations were cyclooxygenase (COX) dependent in BN and SS.13BN rats. In SS rats, hypoxic dilation was restored by indomethacin and abolished by inhibiting cytochrome P-450 epoxygenases, suggesting a role for epoxyeicosatrienoic acids. MCA from SS and SS.13BN rats constricted and MCA from BN rats dilated in response to the stable prostacyclin analog iloprost. MCA from SS.13BN and BN rats (but not SS rats) dilated in response to the prostaglandin E2 receptor agonist butaprost. Hypoxia increased prostacyclin release in cerebral arteries from all the strains, whereas thromboxane A2 production was reduced in BN rat vessels only. These data suggest that SS rats may be less sensitive to vasodilator prostaglandins and that normalization of renin-angiotensin system regulation causes a switch from production of COX-derived vasoconstrictor metabolites (in SS rats) toward NO-dependent relaxation in response to ACh- and prostaglandin-dependent dilation in response to hypoxia in SS.13(BN) rats.
Drenjancevic-Peric
Ines
I
Dept. of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA.
Phillips
Shane A
SA
Falck
John R
JR
Lombard
Julian H
JH
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D020296:Animals, Congenic / Q000235:genetics*; D001794:Blood Pressure; D002536:Cerebral Arteries / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002875:Chromosomes; D004039:Diet, Sodium-Restricted; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D010100:Oxygen / Q000378:metabolism; D010313:Partial Pressure; D051381:Rats; D011914:Rats, Inbred BN / Q000235:genetics*; D020303:Rats, Inbred Dahl / Q000235:genetics*; D014664:Vasodilation / Q000235:genetics / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D000109:Acetylcholine; D010100:Oxygen