Role of endogenous carbon monoxide in central regulation of arterial pressure.
We investigated the contribution of neural mechanisms to the arterial pressure increase produced by zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG), an inhibitor of endogenous carbon monoxide synthesis. The arterial baroreceptor reflex control of heart rate was examined in rats with and without ZnDPBG pretreatment (45 micromol/kg IP) by analysis of the arterial pressure-heart rate relationship during infusions of phenylephrine or sodium nitroprusside to vary arterial pressure. ZnDPBG increased arterial pressure from 110 +/- 3 to 126 +/- 2 mm Hg without eliciting bradycardia. The maximum gain of the heart rate response to changes in arterial pressure was attenuated by ZnDPBG treatment (-1.9 +/- 0.3 versus -4.8 +/- 1.0 bpm/mm Hg). The possibility that ZnDPBG elevates arterial pressure by attenuating baroreceptor reflex function was addressed by comparing the pressor response to ZnDPBG (45 micromol/kg IP) in rats with and without sinoaortic denervation. The pressor effect of ZnDPBG was similar in rats with and without arterial baroreceptor deafferentation, implying that the increase in pressure is not simply the consequence of attenuated baroreceptor reflex function per se. The possibility that ZnDPBG increases arterial pressure via an effect on the nucleus tractus solitarii (NTS) also was investigated. ZnDPBG (1 nmol in 100 nL) injected into the NTS of rats increased arterial pressure from 111 +/- 4 to 126 +/- 5 mm Hg, and this effect was reversed by an ipsilateral microinjection of carbon monoxide into the NTS. Accordingly, the pressor effect of ZnDPBG may rely on inhibition of carbon monoxide production in the NTS. This implies that carbon monoxide formed by brain heme oxygenase plays a role in the central regulation of arterial pressure.
Johnson
R A
RA
Department of Pharmacology, New York Medical College, Valhalla 10595, USA. RobertJ393@aol.com
Colombari
E
E
Colombari
D S
DS
Lavesa
M
M
Talman
W T
WT
Nasjletti
A
A
D000818:Animals; D017704:Baroreflex / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D002248:Carbon Monoxide / Q000378:metabolism* / Q000494:pharmacology; D003905:Deuteroporphyrins / Q000494:pharmacology; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors; D007274:Injections, Intraperitoneal; D008297:Male; D008845:Microinjections; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000494:pharmacology; D017552:Solitary Nucleus / Q000502:physiology
D003905:Deuteroporphyrins; D004338:Drug Combinations; D004791:Enzyme Inhibitors; C060750:zinc deuteroporphyrin IX 2,4-bis(glycol); D012965:Sodium Chloride; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing)