Blood pressure and renal blow flow responses in heme oxygenase-2 knockout mice.
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). To determine the importance of HO-2 in the regulation of blood pressure and renal blood flow (RBF), we treated HO-2 knockout (KO) mice chronically with either ANG II or N(G)-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 RBFs 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(-1)*g(-1) kidney weight in WT, HET, and KO mice. HO-2 KO and HET mice exhibited an attenuated decrease in RBF in response to acute administration of ANG II, while no differences were observed with l-NAME. Our data indicate that blood pressure and RBF responses to increased ANG II or inhibition of nitric oxide are not significantly enhanced in HO-2 KO mice.
Department of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Mississippi 39215, USA. dstec@physiology.umsmed.edu
David E
DE
Stec
Trinity
T
Vera
Megan V
MV
Storm
Gerald R
GR
McLemore
Michael J
MJ
Ryan
D000284:Administration, Oral; D000804:Angiotensin II / Q000008:administration & dosage; D000818:Animals; D001794:Blood Pressure; D006332:Cardiomegaly / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000172:deficiency* / Q000235:genetics; D006973:Hypertension / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D015918:Infusion Pumps, Implantable; D055104:Infusions, Subcutaneous; D007668:Kidney / Q000098:blood supply*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D012079:Renal Circulation; D014655:Vascular Resistance; D014661:Vasoconstriction
D000804:Angiotensin II; D019001:Nitric Oxide Synthase; D006419:Heme Oxygenase (Decyclizing); C105245:heme oxygenase-2; D019331:NG-Nitroarginine Methyl Ester