Autonomic cardiovascular responses to heme oxygenase inhibition in conscious rats.
Carbon monoxide (CO) is produced in the course of heme degradation from biliverdin by heme oxygenase (HO) in various tissues, including the central nervous system. Recent studies suggest the inhibition of HO activity increases arterial pressure mediated by the autonomic nervous system. The present study was designed to investigate the autonomic regulation of cardiovascular responses to inhibition of endogenous CO production by the HO inhibitor Zinc deuteroporphyrin 2, 4-bis glycol (ZnDPBG) by using direct sympathetic nerve recordings in conscious, chronically instrumented rats. ZnDPBG induced increases in mean arterial pressure (MAP) (P<0.05) and renal sympathetic nerve activity (RSNA) (P<0.05) but no significant change in heart rate (P>0.05) in intact rats. In atropine-treated rats, ZnDPBG also induced increases in MAP (P<0.05) and RSNA (P<0.05) but no change in heart rate (P>0.05). In sinoaortic denervated rats, ZnDPBG induced increases in MAP (P<0.05), heart rate (P<0.05), and RSNA (P<0.05). ZnDPBG shifted the baroreflex curve for RSNA upward and to the right, which was characterized by increases in the maximum and minimum response and midpoint pressure without altering the maximum gain. These results indicate that inhibition of HO activity within the central nervous system causes sympathoexcitation, resulting in an increase in arterial pressure. We conclude that the CO/HO system plays an important role in cardiovascular regulation by modulating sympathetic tone.
Hirakawa
Haruhisa
H
Department of Physiology, National Defense Medical College, Saitama, Japan.
Hayashida
Yoshiaki
Y
D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002319:Cardiovascular System / Q000294:innervation; D003905:Deuteroporphyrins / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors* / Q000502:physiology*; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000294:innervation; D008297:Male; D023421:Models, Animal; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology
D003905:Deuteroporphyrins; D004791:Enzyme Inhibitors; C060750:zinc deuteroporphyrin IX 2,4-bis(glycol); D006419:Heme Oxygenase (Decyclizing)