Vasodilator responses to ATP and UTP are not dependent on nitric oxide release, K+ATP channel activation, or the release of vasodilator prostaglandins in the hindlimb vascular bed of the cat

2000 ◽  
Vol 78 (8) ◽  
pp. 612-621 ◽  
Author(s):  
Hunter C Champion ◽  
Philip J Kadowitz
Keyword(s):  
Nitric Oxide ◽  
Nervous System ◽  
Phosphodiesterase Inhibitor ◽  
Inhibitory Effect ◽  
Cyclooxygenase Inhibitors ◽  
Adrenergic System ◽  
Camp Phosphodiesterase ◽  
Nitric Oxide Release ◽  
Vascular Bed ◽  
Adrenergic Nervous System

The effects of the purinergic agonists, ATP, ATPγS, UTP, and 2-Met-Thio AP, were investigated in the hindlimb vascular bed of the cat. Under constant-flow conditions, injections of the purinergic agonists into the perfusion circuit elicited dose-related decreases in perfusion pressure. The order of potency was 2-Met-Thio ATP > ATPγS > ATP > UTP. In contrast, injections of GTPγS, cAMP, UDP, and UMP had no effect. Vasodilator responses to ATP, ATPγS, UTP, and 2-Met-Thio ATP were increased in duration by the cAMP phosphodiesterase inhibitor rolipram, whereas the cGMP phosphodiesterase inhibitor zaprinast had no effect. Responses to the purinergic agonists were not altered by nitric oxide synthase inhibitors, K+ATP channel antagonists, cyclooxygenase inhibitors, or agents that interfere with the actions of the adrenergic nervous system. These data suggest that ATP, ATPγS, UTP, and 2-Met-Thio ATP dilate the hindlimb vascular bed by a direct cAMP-dependent mechanism, and that the release of nitric oxide, vasodilator prostaglandins, K+ATP channel opening, or an inhibitory effect on the adrenergic nervous system play little, if any, role in mediating or modulating responses to the purinergic agonists in the hindlimb circulation of the cat.Key words: purinergic agonists, P2 purinergic receptors, cAMP-dependent vasodilator activity, adrenergic system, nitric oxide prostaglandins.

Vasodilator responses to adenosine and hyperemia are mediated by A1 and A2 receptors in the cat vascular bed

2002 ◽  
Vol 282 (6) ◽  
pp. R1696-R1709 ◽  
Author(s):  
Trinity J. Bivalacqua ◽  
Hunter C. Champion ◽  
David G. Lambert ◽  
Philip J. Kadowitz
Keyword(s):  
Nitric Oxide ◽  
Reactive Hyperemia ◽  
Phosphodiesterase Inhibitor ◽  
Receptor Antagonists ◽  
Camp Phosphodiesterase ◽  
Nitric Oxide Synthase Inhibitor ◽  
Vascular Bed ◽  
S Period ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Hemodynamic responses to adenosine, the A1 receptor agonists N 6-cyclopentyladenosine (CPA) and adenosine amine congener (ADAC), and the A2 receptor agonist 5′-( N-cyclopropyl)-carboxamido-adenosine (CPCA) were investigated in the hindquarter vascular bed of the cat under constant-flow conditions. Injections of adenosine, CPA, ADAC, CPCA, ATP, and adenosine 5′- O-(3-thiotriphosphate) (ATPγS) into the perfusion circuit induced dose-related decreases in perfusion pressure. Vasodilator responses to the A1 agonists were reduced by the A1 receptor antagonists KW-3902 and CGS-15943, whereas responses to CPCA were reduced by the A2 antagonist KF-17837. Vasodilator responses to adenosine were reduced by KW-3902, CGS-15943, and by KF-17837, suggesting a role for both A1 and A2 receptors. Vasodilator responses to ATP and the nonhydrolyzable ATP analog ATPγS were not attenuated by CGS-15943 or KF-17837. After treatment with the nitric oxide synthase inhibitor N ω-nitro-l-arginine methyl ester, the cyclooxygenase inhibitor sodium meclofenamate, or the ATP-dependent K+ (K[Formula: see text]) channel antagonists U-37883A or glibenclamide, responses to adenosine and ATP were not altered. Responses to adenosine, CPA, and CPCA were increased in duration by rolipram, a type 4 cAMP phosphodiesterase inhibitor, but were not altered by zaprinast, a type 5 cGMP phosphodiesterase inhibitor. When blood flow was interrupted for a 30-s period, the magnitude and duration of the reactive vasodilator response were reduced by A1 and A2 receptor antagonists. These data suggest that vasodilator responses to adenosine and the A1and A2 agonists studied are not dependent on the release of cyclooxygenase products, nitric oxide, or the opening of K[Formula: see text] channels in the regional vascular bed of the cat. The present data suggest a role for cAMP in mediating responses to adenosine and suggest that vasodilator responses to adenosine and to reactive hyperemia are mediated in part by A1 and A2 receptors in the hindquarter vascular bed of the cat.

scholarly journals Modulation of macrophage activation by prostaglandins

1996 ◽  
Vol 5 (1) ◽  
pp. 14-17 ◽  
Author(s):  
L. Sautebin ◽  
R. Carnuccio ◽  
F. D'Acquisto ◽  
M. Di Rosa
Keyword(s):  
Nitric Oxide ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Phosphodiesterase Inhibitor ◽  
Inhibitory Effect ◽  
Prostaglandin E ◽  
Tumour Necrosis Factor Α ◽  
Nitric Oxide Release ◽  
Factor Α ◽  
Necrosis Factor

The effect of prostaglandtn E2, iloprost and cAMP on both nitric oxide and tumour necrosis factor-α release in J774 macrophages has been studied. Both prostaglandin E2and iloprost inhibited, in a concentration-dependent fashion, the lipopolysaccharide-induced generation of nitric oxide and tumour necrosis factor-α. The inhibitory effect of these prostanoids seems to be mediated by an increase of the second messenger cAMP since it was mimicked by dibutyryl cAMP and potentiated by the selective type IV phosphodiesterase inhibitor RO-20-1724. Our results suggest that the inhibition of nitric oxide release by prostaglandin E2and iloprost in lipopolysaccharide-activated J774 macrophages may be secondary to the inhibition of tumour necrosis factor-α generation, which in turn is likely to be mediated by cAMP.

Adrenomedullin-(22-52) antagonizes vasodilator responses to CGRP but not adrenomedullin in the cat

1997 ◽  
Vol 272 (1) ◽  
pp. R234-R242 ◽  
Author(s):  
H. C. Champion ◽  
J. A. Santiago ◽  
W. A. Murphy ◽  
D. H. Coy ◽  
P. J. Kadowitz
Keyword(s):  
Receptor Antagonist ◽  
Phosphodiesterase Inhibitor ◽  
Inhibitory Effects ◽  
Camp Phosphodiesterase ◽  
Cyclic Monophosphate ◽  
Related Peptide ◽  
Vascular Bed ◽  
Calcitonin Gene ◽  
Adrenergic Nervous System ◽  
Cgrp Receptor Antagonist

The effects of adrenomedullin (ADM)-(22-52), a putative ADM receptor antagonist, on vasodilator responses to ADM and the structurally related peptide, calcitonin gene-related peptide (CGRP), were investigated in the hindlimb vascular bed of the cat under constant-flow conditions. ADM-(22-52) had no significant effect on hindlimb perfusion pressure when injected in doses up to 120 nmol; after administration of ADM-(22-52), vasodilator responses to ADM were unchanged, whereas vasodilator responses to CGRP were inhibited. The inhibitory effects of ADM-(22-52) on responses to CGRP were selective and reversible and were similar to the inhibitory effects of the CGRP antagonist CGRP-(8-37). Hindlimb vasodilator responses to CGRP and to ADM were increased in duration by the adenosine 3',5'-cyclic monophosphate (cAMP) phosphodiesterase inhibitor rolipram but were not altered by inhibitors of guanosine 3',5'-cyclic monophosphate phosphodiesterase, nitric oxide synthetase, K(+)-ATP channels, the cyclooxygenase pathway, or the adrenergic nervous system. These results demonstrate that ADM-(22-52) is a selective CGRP receptor antagonist in the hindlimb vascular bed of the cat. The present data suggest that vasodilator responses to CGRP and ADM are mediated by different receptors but that these peptides dilate the hindlimb vascular bed of the cat by a similar cAMP-dependent mechanism.

Inhibitory effect of melatonin on nitric oxide synthase in rat enteric nervous system

2001 ◽  
Vol 120 (5) ◽  
pp. A176-A176
Author(s):  
P KOPPITZ ◽  
M STORR ◽  
D SAUR ◽  
M KURJAK ◽  
H ALLESCHER
Keyword(s):  
Nitric Oxide ◽  
Nervous System ◽  
Nitric Oxide Synthase ◽  
Enteric Nervous System ◽  
Inhibitory Effect ◽  
Oxide Synthase

Evidence for α-adrenergic receptors mediated TSH release in men

1980 ◽  
Vol 95 (2) ◽  
pp. 172-176 ◽  
Author(s):  
Stefan Zgliczyński ◽  
Marek Kaniewski
Keyword(s):  
Nervous System ◽  
Healthy Volunteers ◽  
Adrenergic Receptors ◽  
Bolus Injection ◽  
Physiological Mechanism ◽  
Adrenergic System ◽  
Trh Stimulation ◽  
Tsh Secretion ◽  
Adrenergic Nervous System

Abstract. In order to elucidate the role of the adrenergic nervous system in the mechanism of TSH release in men the effects of α- and β-receptors blocking agents were studied in 11 healthy volunteers. Phentolamine administetred iv as a bolus injection in a dose of 10 mg, significantly lowered the TSH release in basal condition and in response to TRH stimulation. However, propranolol in a dose of 0.1 mg/kg administered in the same fashion as phentolamine had no effect on the TSH secretion. The results obtained suggest that the α-receptors of the adrenergic system are involved in the physiological mechanism which stimulates TSH release in men.

Inhibitory effect of experimental colitis on fluid absorption in rat jejunum: role of the enteric nervous system, VIP, and nitric oxide

2006 ◽  
Vol 290 (2) ◽  
pp. G262-G268 ◽  
Author(s):  
Fadi H. Mourad ◽  
Kassem A. Barada ◽  
Nadine A. Bou Rached ◽  
Carmen I. Khoury ◽  
Nayef E. Saadé ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nervous System ◽  
Enteric Nervous System ◽  
Experimental Colitis ◽  
Inhibitory Effect ◽  
Fluid Absorption ◽  
Receptor Antagonism ◽  
Chemical Colitis

Impairment of small intestinal absorption has been described in patients with ulcerative colitis and in animal models of experimental colitis. The pathophysiology of this dysfunction has not been elucidated. The aim of this study was to investigate the effect of chemical colitis on jejunal fluid absorption and determine the role of the enteric nervous system and some putative neurotransmitters. In a rat model of iodoacetamide-induced colitis, jejunal net fluid absorption was evaluated by the in vivo single-pass perfusion technique. The effects of 1) tetrodotoxin (TTX), 2) benzylalkonium chloride (BAC), 3) capsaicin, 4) vasoactive intestinal polypeptide (VIP) antagonism, 5) nitric oxide (NO) synthase (NOS) inhibition, and 6) 5-hydroxytryptamine type 3 and 4 (5-HT3 and 5-HT4) receptor antagonism on the changes in fluid movement were investigated. A significant decrease in jejunal net fluid absorption was found 2 and 4 days after colitis induction: 26 (SD 14) and 28 (SD 19) μl·min−1·g dry intestinal wt−1, respectively [ P < 0.0002 compared with sham rats at 61 (SD 6.5) μl·min−1·g dry intestinal wt−1]. No histological changes were evident in jejunal sections. TTX and BAC reversed this decrease in fluid absorption: 54 (SD 13) and 44 (SD 14) μl·min−1·g dry intestinal wt−1 ( P = 0.0005 and P = 0.019, respectively, compared with colitis). Ablation of capsaicin-sensitive primary afferent fibers had a partial effect: 45 (SD 5) μl·min−1·g dry intestinal wt−1 ( P = 0.001 and P = 0.003 compared with colitis and sham, respectively). Constitutive and neuronal NOS inhibition and VIP antagonism returned jejunal net fluid absorption to normal values: 66 (SD 19), 61 (SD 5), and 56 (SD 14) μl·min−1·g dry intestinal wt−1, respectively. 5-HT3 and 5-HT4 receptor antagonism had no effect. Chemical colitis is associated with a significant decrease in jejunal net fluid absorption. This decrease is neurally mediated and involves VIP- and NO-related mechanisms.

Inhibitory effect of melatonin on nitric oxide synthase in rat enteric nervous system

2001 ◽  
Vol 120 (5) ◽  
pp. A176
Author(s):  
Patrick B. Koppitz ◽  
Martin A. Storr ◽  
Dieter Saur ◽  
Manfred Kurjak ◽  
Hans-Dieter Allescher
Keyword(s):  
Nitric Oxide ◽  
Nervous System ◽  
Nitric Oxide Synthase ◽  
Enteric Nervous System ◽  
Inhibitory Effect ◽  
Oxide Synthase

Proadrenomedullin NH2-terminal 20 peptide has direct vasodilator activity in the cat

1997 ◽  
Vol 272 (4) ◽  
pp. R1047-R1054 ◽  
Author(s):  
H. C. Champion ◽  
W. A. Murphy ◽  
D. H. Coy ◽  
P. J. Kadowitz
Keyword(s):  
Phosphodiesterase Inhibitor ◽  
Sympathetic Nerves ◽  
Adrenergic Nerve ◽  
Camp Phosphodiesterase ◽  
Cyclic Monophosphate ◽  
Vascular Bed ◽  
Vasodilator Activity ◽  
Calcitonin Gene ◽  
Cgrp Receptor Antagonist ◽  
Oxide Synthase

The mechanism by which proadrenomedullin NH2-terminal 20 peptide (PAMP) decreases vascular resistance was investigated in the hindlimb vascular bed in the cat. Injections of PAMP, a shortened form of the peptide PAMP-(12-20), and adrenomedullin (ADM) into the hindlimb perfusion circuit elicit dose-related decreases in perfusion pressure. The order of potency was ADM > PAMP > PAMP-(12-20), and the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8-37) had no effect on vasodilator responses to PAMP or ADM. Vasodilator responses to PAMP were increased in duration by the adenosine 3',5'-cyclic monophosphate (cAMP) phosphodiesterase inhibitor Rolipram, whereas inhibitors of nitric oxide synthase and guanosine 3',5'-cyclic monophosphate phosphodiesterase had no effect. Vasodilator responses to PAMP were not altered by treatment with alpha-receptor or adrenergic nerve terminal blocking agents and were similar in innervated and denervated hindlimb preparations. Responses to PAMP were similar when vasoconstrictor tone was increased by stimulation of the sympathetic nerves or infusion of phenylephrine and were not altered by the passage of time. These data suggest that PAMP dilates the hindlimb vascular bed by a direct cAMP-dependent mechanism and that inhibition of norepinephrine release plays little if any role in mediating responses to the peptide in the regional vascular bed of the cat.

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