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Inhibition by zinc protoporphyrin-IX of receptor-mediated relaxation of the rat aorta in a manner distinct from inhibition of haem oxygenase

Ny, L; Andersson, K E LU and Grundemar, L LU (1995) In British Journal of Pharmacology 115(1). p.186-190
Abstract

1. Carbon monoxide (CO), produced by haem oxygenase through degradation of haem, has been claimed to be a neuromessenger and a possible regulator of vascular tone. We examined whether the haem oxygenase inhibitor, zinc protoporphyrin-IX (ZnPP) and other porphyrins affect the relaxation evoked by various agents in the rat isolated aorta. 2. Pretreatment with ZnPP (0.1 mM) virtually abolished the relaxation evoked by vasoactive intestinal peptide (VIP) and atrial natriuretic peptide (ANP). ZnPP also evoked a rightward shift of the concentration-response curve for the relaxation induced by acetylcholine. 3. In contrast, ZnPP did not affect the relaxation evoked by forskolin and 3-morpholino-sydnonimine, agents which directly activate... (More)

1. Carbon monoxide (CO), produced by haem oxygenase through degradation of haem, has been claimed to be a neuromessenger and a possible regulator of vascular tone. We examined whether the haem oxygenase inhibitor, zinc protoporphyrin-IX (ZnPP) and other porphyrins affect the relaxation evoked by various agents in the rat isolated aorta. 2. Pretreatment with ZnPP (0.1 mM) virtually abolished the relaxation evoked by vasoactive intestinal peptide (VIP) and atrial natriuretic peptide (ANP). ZnPP also evoked a rightward shift of the concentration-response curve for the relaxation induced by acetylcholine. 3. In contrast, ZnPP did not affect the relaxation evoked by forskolin and 3-morpholino-sydnonimine, agents which directly activate adenylate and guanylate cyclase, respectively. 4. Although, less effective than ZnPP, tin protoporphyrin-IX (SnPP; 0.1 mM) and protoporphyrin-IX (PP; 0.1 mM) also attenuated the VIP-evoked relaxation. 5. The elevation of cyclic AMP and cyclic GMP levels evoked by VIP and ANP, respectively, were abolished by pretreatment with ZnPP (0.1 mM). 6. ZnPP, SnPP and PP did not affect the contraction evoked by phenylephrine. 7. The results show that ZnPP inhibits relaxation induced by VIP, ANP and acetylcholine, probably by interfering with membrane receptor-coupled signal transduction pathways. This inhibition does not seem to be dependent upon inhibition of haem oxygenase. The lack of specificity of the haem oxygenase inhibiting metalloporphyrins makes them less suitable as pharmacological tools in the investigation of a messenger role for CO.

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published
subject
keywords
Animals, Aorta, Cyclic AMP/metabolism, Cyclic GMP/metabolism, Female, Heme Oxygenase (Decyclizing)/antagonists & inhibitors, In Vitro Techniques, Muscle Relaxation/drug effects, Muscle, Smooth, Vascular/drug effects, Porphyrins/pharmacology, Protoporphyrins/pharmacology, Rats, Rats, Sprague-Dawley, Signal Transduction, Vasodilation/drug effects
in
British Journal of Pharmacology
volume
115
issue
1
pages
186 - 190
publisher
The British Pharmacological Society
external identifiers
  • scopus:0029014720
ISSN
0007-1188
DOI
10.1111/j.1476-5381.1995.tb16337.x
language
English
LU publication?
no
id
efdd5b00-e686-40a5-ba45-b25498b463d1
date added to LUP
2019-09-03 14:04:56
date last changed
2019-09-08 04:43:20
@article{efdd5b00-e686-40a5-ba45-b25498b463d1,
  abstract     = {<p>1. Carbon monoxide (CO), produced by haem oxygenase through degradation of haem, has been claimed to be a neuromessenger and a possible regulator of vascular tone. We examined whether the haem oxygenase inhibitor, zinc protoporphyrin-IX (ZnPP) and other porphyrins affect the relaxation evoked by various agents in the rat isolated aorta. 2. Pretreatment with ZnPP (0.1 mM) virtually abolished the relaxation evoked by vasoactive intestinal peptide (VIP) and atrial natriuretic peptide (ANP). ZnPP also evoked a rightward shift of the concentration-response curve for the relaxation induced by acetylcholine. 3. In contrast, ZnPP did not affect the relaxation evoked by forskolin and 3-morpholino-sydnonimine, agents which directly activate adenylate and guanylate cyclase, respectively. 4. Although, less effective than ZnPP, tin protoporphyrin-IX (SnPP; 0.1 mM) and protoporphyrin-IX (PP; 0.1 mM) also attenuated the VIP-evoked relaxation. 5. The elevation of cyclic AMP and cyclic GMP levels evoked by VIP and ANP, respectively, were abolished by pretreatment with ZnPP (0.1 mM). 6. ZnPP, SnPP and PP did not affect the contraction evoked by phenylephrine. 7. The results show that ZnPP inhibits relaxation induced by VIP, ANP and acetylcholine, probably by interfering with membrane receptor-coupled signal transduction pathways. This inhibition does not seem to be dependent upon inhibition of haem oxygenase. The lack of specificity of the haem oxygenase inhibiting metalloporphyrins makes them less suitable as pharmacological tools in the investigation of a messenger role for CO.</p>},
  author       = {Ny, L and Andersson, K E and Grundemar, L},
  issn         = {0007-1188},
  keyword      = {Animals,Aorta,Cyclic AMP/metabolism,Cyclic GMP/metabolism,Female,Heme Oxygenase (Decyclizing)/antagonists & inhibitors,In Vitro Techniques,Muscle Relaxation/drug effects,Muscle, Smooth, Vascular/drug effects,Porphyrins/pharmacology,Protoporphyrins/pharmacology,Rats,Rats, Sprague-Dawley,Signal Transduction,Vasodilation/drug effects},
  language     = {eng},
  number       = {1},
  pages        = {186--190},
  publisher    = {The British Pharmacological Society},
  series       = {British Journal of Pharmacology},
  title        = {Inhibition by zinc protoporphyrin-IX of receptor-mediated relaxation of the rat aorta in a manner distinct from inhibition of haem oxygenase},
  url          = {http://dx.doi.org/10.1111/j.1476-5381.1995.tb16337.x},
  volume       = {115},
  year         = {1995},
}