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Stimulation of capsaicin-sensitive sensory fibers induces vasodilation in rat mesenteric bed
145
STIMULATION OF C A P S A I C I N - S E N S I T I V E SENSORY F I B E R S VASODILATION I N RAT MESENTERIC BED Francesca
PERRETTI 1 ,
Pierangelo
GEPPETTI 2 a n d
1 Department of Pharmacology - MALESCI S . p . A . Via Porpora, 22 - FLORENCE ( I T A L Y ) 2 Department of Internal University of Florence FLORENCE ( I T A L Y )
Medicine and Clinical - Viale Morgagni, 65
INDUCES
Stefano
MANZINI 1
-
Pharmacology
Capsaicin vasodilatory properties were investigated in rat mesenteric bed, which has been described to be densely endowed with a network of neuropeptide-containing capsaicin-sensitive sensory fibers (1). Intraand extra-luminal capsaicin ( 1 0 nM - 1 ~M) a d m i n i s t r a t i o n resulted in a potent and concentration-dependent inhibition of norepinephrine (NE)-induced tonic vasoconstriction, reaching a maximal reduction o f 76 + 9 mmHg ( 8 2 ~ ) w i t h c a p s a i c i n O . 1 ~M. On t h e c o n t r a r y , w h e n h i g h K+ m e d i u m ( 2 0 - 4 0 - 6 0 mM) w a s u s e d , to induce tonic vasoconstriction, capsaicin ( 0 . 1 ~H) e x e r t e d vasorelaxant action w h i c h w a s w e a k e r t h a n t o w a r d NE a n d inversely related t o K+ c o n c e n t J r a t i o n . Capsaicin induced relaxation was virtually abolished after "in vitro" capsaicin desensitization and markedly reduced in preparations obtained from rats neonatally pretreated with capsaicin. Capsaicin actions were unaffected by atropine, guanethidine, propranolol, hexamethonium or tetrodotoxin but abolished by the proteolytie enzyme o-chymotrypsin (1 U/ml). In addition capsaicin effects were partially endothelium-dependent. In fact, when endothelium was removed (by means of collagenase 0.2~) capsaicin ( 0 . 1 ~M) - i n d u c e d vasorelaxation was reduced f r o m 6 2 . 2 + 5 . 8 t o 2 6 . 7 + 5 . 9 mmHg ( P < 0 . 0 5 ) . Although after capsaicin perfusion, a small increase in substance P-like immunoreactivity outflow was detected, substance P ( 1 ~M) b a r e l y affected NE-induced tonic vasoconstriction (its maximal relaxant effect was 4.8 + 1.4 mmHg). Neurokinin A (1 ~M) d i d n o t e x h i b i t any vasodilatory properties. On t h e o t h e r hand calcitonin gene-related peptide ( 0 . 0 1 ~M) i n j e c t i o n elicited a prompt and marked relaxation which underwent desensitization; however no cross desensitization with capsaicin action was observed. In conclusion, in rat mesenterie bed, capsaicin exerts a potent and selective relaxant effect, largely ascribable to stimulation of sensory nerve endings. Albeit the vasorelaxant neuropeptide(s) involved remains to be established, local peripheral function of these fibers might play an important role in control of intestinal blood flow.
1.
WHARTON
et
al.
(1986)
J
Auton
Nerv
Syst
16:289-309
STIMULATION OF C A P S A I C I N - S E N S I T I V E SENSORY F I B E R S VASODILATION I N RAT MESENTERIC BED Francesca
PERRETTI 1 ,
Pierangelo
GEPPETTI 2 a n d
1 Department of Pharmacology - MALESCI S . p . A . Via Porpora, 22 - FLORENCE ( I T A L Y ) 2 Department of Internal University of Florence FLORENCE ( I T A L Y )
Medicine and Clinical - Viale Morgagni, 65
INDUCES
Stefano
MANZINI 1
-
Pharmacology
Capsaicin vasodilatory properties were investigated in rat mesenteric bed, which has been described to be densely endowed with a network of neuropeptide-containing capsaicin-sensitive sensory fibers (1). Intraand extra-luminal capsaicin ( 1 0 nM - 1 ~M) a d m i n i s t r a t i o n resulted in a potent and concentration-dependent inhibition of norepinephrine (NE)-induced tonic vasoconstriction, reaching a maximal reduction o f 76 + 9 mmHg ( 8 2 ~ ) w i t h c a p s a i c i n O . 1 ~M. On t h e c o n t r a r y , w h e n h i g h K+ m e d i u m ( 2 0 - 4 0 - 6 0 mM) w a s u s e d , to induce tonic vasoconstriction, capsaicin ( 0 . 1 ~H) e x e r t e d vasorelaxant action w h i c h w a s w e a k e r t h a n t o w a r d NE a n d inversely related t o K+ c o n c e n t J r a t i o n . Capsaicin induced relaxation was virtually abolished after "in vitro" capsaicin desensitization and markedly reduced in preparations obtained from rats neonatally pretreated with capsaicin. Capsaicin actions were unaffected by atropine, guanethidine, propranolol, hexamethonium or tetrodotoxin but abolished by the proteolytie enzyme o-chymotrypsin (1 U/ml). In addition capsaicin effects were partially endothelium-dependent. In fact, when endothelium was removed (by means of collagenase 0.2~) capsaicin ( 0 . 1 ~M) - i n d u c e d vasorelaxation was reduced f r o m 6 2 . 2 + 5 . 8 t o 2 6 . 7 + 5 . 9 mmHg ( P < 0 . 0 5 ) . Although after capsaicin perfusion, a small increase in substance P-like immunoreactivity outflow was detected, substance P ( 1 ~M) b a r e l y affected NE-induced tonic vasoconstriction (its maximal relaxant effect was 4.8 + 1.4 mmHg). Neurokinin A (1 ~M) d i d n o t e x h i b i t any vasodilatory properties. On t h e o t h e r hand calcitonin gene-related peptide ( 0 . 0 1 ~M) i n j e c t i o n elicited a prompt and marked relaxation which underwent desensitization; however no cross desensitization with capsaicin action was observed. In conclusion, in rat mesenterie bed, capsaicin exerts a potent and selective relaxant effect, largely ascribable to stimulation of sensory nerve endings. Albeit the vasorelaxant neuropeptide(s) involved remains to be established, local peripheral function of these fibers might play an important role in control of intestinal blood flow.
1.
WHARTON
et
al.
(1986)
J
Auton
Nerv
Syst
16:289-309