Heme Oxygenase-1 Induction Does Not Improve Vascular Relaxation in Angiotensin II Hypertensive Mice
| Autor: | Gerald R. McLemore, Silvia Kelsen, David E. Stec, Michael J. Ryan, John M. Rimoldi, Trinity Vera, Rama S.V. Gadepalli |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
medicine.medical_specialty Endothelium Thromboxane Protoporphyrins Vasodilation Peptide hormone Article Mice Internal medicine Internal Medicine medicine Animals Vasoconstrictor Agents Drug Interactions Aorta business.industry Angiotensin II COPP Enzyme Activation Mice Inbred C57BL Heme oxygenase Endocrinology medicine.anatomical_structure Hypertension Endothelium Vascular Sodium nitroprusside business Heme Oxygenase-1 medicine.drug |
| Zdroj: | American Journal of Hypertension. 21:189-193 |
| ISSN: | 1941-7225 0895-7061 |
| Popis: | 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 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 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 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. |
| Databáze: | OpenAIRE |
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