Heme oxygenase-1 induction does not improve vascular relaxation in angiotensin II hypertensive mice.
BACKGROUND
Induction of heme oxygenase-1 (HO-1) attenuates the development of angiotensin II (Ang II)-dependent hypertension in mice. However, the mechanism by which HO-1 lowers blood pressure in this model is not clear. This study was designed to determine whether induction of HO-1 results in an improvement in vascular relaxation in Ang II hypertensive mice.


METHODS
Mice were treated with either of the vehicles (control), the HO-1 inducer cobalt protoporphyrin (CoPP;50 mg/kg), Ang II(1 microg/kg/min, 14 days), or Ang II + CoPP. CoPP was administered as a single bolus dose 2 days prior to subcutaneous implantation of the osmotic minipump containing Ang II. Vascular relaxation was examined in isolated carotid arteries precontracted with the thromboxane mimetic U46619 (0.4 microg/ml).


RESULTS
Endothelial dependent relaxation to acetylcholine (ACh; 1 micromol/l) was significantly impaired in Ang II-treated mice compared to control mice (56 +/- 3% vs. 40 +/- 4%, P < 0.05, n > or = 6). Similarly, endothelial independent relaxation to sodium nitroprusside (SNP; 1 micromol/l) was significantly impaired in Ang II mice (56 +/- 6% vs. 28 +/- 6%, P < 0.05, n > or = 6). Relaxation in response to the carbon monoxide donor, CORM-A1 (100 micromol/l), was attenuated after Ang II treatment (75 +/- 7% vs. 59 +/- 7%,P < 0.05, n > or = 6). CoPP treatment induced HO-1 but not HO-2 protein in the aorta, as measured by western blot analysis. CoPP treatment had no effect on vascular responses in control mice and did not improve ACh (26 +/- 5%, n = 15), SNP (23 +/- 4%, n = 15), or CORM-A1 (46 +/- 7%, n = 10) dependent relaxation in Ang II treated mice.


CONCLUSIONS
These results suggest that induction of HO-1 lowers Ang II-dependent hypertension through a mechanism independent of improved vascular relaxation.
Stec
David E
DE
Department of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Mississippi, USA. dstec@physiology.umsmed.edu
Vera
Trinity
T
McLemore
Gerald R
GR
Kelsen
Silvia
S
Rimoldi
John M
JM
Gadepalli
Rama S V
RS
Ryan
Michael J
MJ
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011524:Protoporphyrins / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D011524:Protoporphyrins; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C007095:cobaltiprotoporphyrin; D051547:Heme Oxygenase-1