Submitted on June 8, 2009
Revised on October 19, 2009
Accepted on October 19, 2009
Blood pressure and renal blood flow responses in heme oxygenase-2 knockout mice
David E. Stec1*, Trinity Vera1, Megan V. Storm1, Gerald R McLemore, Jr.1, and Michael J Ryan1
1 University of Mississippi Medical Center
* To whom correspondence should be addressed. E-mail: dstec{at}physiology.umsmed.edu.
Heme oxygenase (HO) is the enzyme responsible for the breakdown of heme generating carbon monoxide (CO) and biliverdin in this process. HO-2 is the constitutively expressed isoform in most tissues such as the kidney and vasculature. CO generated by HO is believed to be an important vasodilator in the renal circulation along with another gas, nitric oxide (NO). In order to determine the importance of HO-2 in the regulation of blood pressure and renal blood flow, we treated HO-2 knockout (KO) mice chronically with either Angiotensin II (Ang II) or L-NG-Nitroarginine methyl ester (L-NAME). Basal blood pressures were not different between wild-type (WT), heterozygous (HET), or KO mice and averaged 113 ± 3, vs. 115 ± 2, vs.116 ± 2 mmHg. Similar increases in blood pressure to chronic Ang II as well as L-NAME treatment were observed in all groups with blood pressures increasing an average of 30 mmHg in response to Ang II and 15 mmHg in response to L-NAME. Basal renal blood flows were not different between the groups averaging 6.0 ± 0.5 (n=6), vs. 4.8 ± 0.6 (n=10), vs. 5.8 ± 0.7 (n=6) ml/min/g kidney weight in WT, HET, and KO mice. HO-2 KO and HET mice exhibited an attenuated decrease in renal blood flow in response to acute administration of Ang II while no differences were observed with L-NAME. Our data indicate that blood pressure and renal blood flow responses to increased Ang II or inhibition of NO are not significantly enhanced in HO-2 KO mice.
