Carbon monoxide regulates blood pressure cooperatively with nitric oxide in hypertensive rats.

Abstract

Both carbon monoxide (CO), the product of heme oxygenase (HO), and nitric oxide (NO) elevate cyclic guanosine monophosphate levels in smooth muscle cells, leading to relaxation of the vessels. We examined the hypothesis that the effect of CO in regulating blood pressure could be augmented in hypertension where the function and/or production of NO is impaired. We used two hypertensive models, a spontaneously hypertensive rat (SHR), and a Wistar Kyoto rat (WKY) which was given the NO synthase (NOS) inhibitor N(omega)-nitro- L-arginine (L-NNA). In these hypertensive rats, we examined HO gene expression with Northern blot analysis, guanosine 3',5'-monophosphate (cGMP) levels with enzyme-linked immunosorbent assay of each organ, and the response of blood pressure to treatment with an HO substrate (hemin, 23 micromol/kg body weight, i.p.) or HO inhibitor (zinc or tin protoporphyrin-IX; ZnPP or SnPP, 50 micromol/kg body weight i.p. or s.c.), for 4 or 8 consecutive days with plethysmography. Northern blot analysis showed that HO-1 and -2 mRNA levels in the left ventricle, aorta, kidney, and soleus muscle in the hypertensive rats were 2-5 times higher than those in control normotensive WKYrats. In contrast, both HO mRNA levels in the gastrocnemius muscle in the hypertensive rats were similar to those in control WKYrats. As to whether the HO/CO system contributes to the regulation of blood pressure, ZnPP or SnPP increased and hemin decreased systolic blood pressure (SBP), respectively, in the hypertensive rats (P < 0.01), but not in WKYrats, accompanied with changes in cGMP in each organ of the hypertensive rats. The effect of CO in the regulation of blood pressure is augmented, resulting in increased expression of HO gene when the function and/or production of NO is impaired.

• Authors: Masayuki Ushiyama, Toshisuke Morita, Shigehiro Katayama
• Journal: Heart and vessels (Heart Vessels) Vol. 16 Issue 5 Pg. 189-95 (Jul 2002) ISSN: 0910-8327 [Print] Japan
• PMID: 12181592 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Protoporphyrins
• RNA, Messenger
• zinc protoporphyrin
• Nitroarginine
• Nitric Oxide
• Hemin
• Carbon Monoxide
• Nitric Oxide Synthase
• Heme Oxygenase (Decyclizing)
• Cyclic GMP

Topics

• Animals
• Aorta (chemistry, drug effects, metabolism)
• Blood Pressure (drug effects)
• Blotting, Northern
• Carbon Monoxide (pharmacology, urine)
• Cyclic GMP (analysis)
• Enzyme Inhibitors (pharmacology)
• Heme Oxygenase (Decyclizing) (antagonists & inhibitors, genetics, metabolism)
• Hemin (pharmacology)
• Hypertension (drug therapy, metabolism, physiopathology)
• Kidney (chemistry, drug effects, metabolism)
• Male
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase (antagonists & inhibitors)
• Nitroarginine (pharmacology)
• Protoporphyrins (pharmacology)
• RNA, Messenger (genetics, metabolism)
• Rats
• Rats, Inbred SHR
• Rats, Inbred WKY