NO release and the opening of K+ATP channels mediate vasodilator responses to histamine in the cat

1997 ◽  
Vol 273 (2) ◽  
pp. H928-H937 ◽  
Author(s):  
H. C. Champion ◽  
P. J. Kadowitz
Keyword(s):  
Nitric Oxide ◽  
Phosphodiesterase Inhibitor ◽  
Receptor Activation ◽  
K Channel ◽  
Flow Conditions ◽  
Nitric Oxide Synthase Inhibitor ◽  
Vascular Bed ◽  
H3 Receptor ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Responses to histamine were investigated in the hindlimb vascular bed of the cat under constant-flow conditions. Injections of histamine, the H1 agonist HTMT, the H2 agonist dimaprit, and the H3 agonist R(-)-alpha-methylhistamine caused dose-related decreases in hindlimb perfusion pressure. Pyrilamine reduced the responses to histamine and HTMT by approximately 80%, whereas cimetidine reduced the responses to histamine by 20% and to dimaprit by approximately 50%. The H3-receptor antagonist thioperamide reduced the responses to R(-)-alpha-methylhistamine by approximately 60% but was without effect on the other histamine agonists. These data suggest the presence of H1, H2, and H3 receptors in the hindlimb vascular bed of the cat, that histamine acts, for the most part, by stimulating H1 receptors, and that H3-receptor activation is not involved in mediating the responses to histamine. The responses to histamine and the H1-, H2-, and H3-receptor agonists were significantly reduced by a nitric oxide synthase inhibitor and enhanced in duration by the guanosine 3', 5'-cyclic monophosphate (cGMP)-selective phosphodiesterase inhibitor zaprinast, suggesting that the responses are mediated, in part, by the release of nitric oxide and an increase in cGMP levels. The responses to histamine agonists but not to nitric oxide donors were significantly reduced by the nonselective K(+)-channel antagonist tetraethylammonium. The responses to histamine and the H1, H2, and H3 agonists were not affected by the cyclooxygenase inhibitor meclofenamate. The responses to histamine and HTMT are also reduced 30-50% by U-37883A, an ATP-sensitive K+ (K+ATP)-channel antagonist, at a time when the responses to the H2 and H3 agonists were unaltered. The present data suggest that vasodilation of the hindlimb vascular bed in response to H1-, H2-, and H3-receptor activation is mediated by a tetraethylammonium-sensitive mechanism that is associated with the release of nitric oxide and an increase in cGMP levels. These data further suggest that the response to H1-receptor activation is mediated by the complementary, yet independent, release of nitric oxide and the opening of a K+ATP channel.

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.

Neurogenic Dural Protein Extravasation Induced by Meta-Chlorophenylpiperazine (Mcpp) Involves Nitric Oxide and 5-HT2B Receptor Activation

Cephalalgia ◽  
2003 ◽  
Vol 23 (2) ◽  
pp. 117-123 ◽  
Author(s):  
KW Johnson ◽  
DL Nelson ◽  
DK Dieckman ◽  
DB Wainscott ◽  
VL Lucaites ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Receptor Antagonist ◽  
Receptor Activation ◽  
Trigeminal System ◽  
Nitric Oxide Synthase Inhibitor ◽  
Protein Extravasation ◽  
Plasma Protein Extravasation ◽  
Synthase Inhibitor ◽  
Oxide Synthase ◽  
Stimulation Of

The compound m-chlorophenylpiperazine (mCPP), which is known to trigger migraine-like head pain in some subjects, was evaluated for its ability to induce dural plasma protein extravasation (PPE) in guinea pigs. Intravenous mCPP dose-dependently increased PPE. This effect was inhibited by non-selective 5-HT2 receptor antagonists (methysergide, LY53857, LY215840), by a peripherally restricted 5-HT2 receptor antagonist (xylamidine) and by a 5-HT2B selective receptor antagonist (LY202146). These data suggests that peripheral 5-HT2B receptors mediate mCPP-induced PPE. The nitric oxide synthase inhibitor L-NAME and 5-HT1 agonist sumatriptan also blocked mCPP-induced PPE, suggesting a role for nitric oxide (NO) and the trigeminal system, respectively. NO release has been linked to activation of the 5-HT2B receptor on the vascular endothelium. However, LY202146 did not block PPE induced by electrical stimulation of the trigeminal ganglion. These data are consistent with activation of peripheral 5-HT2B receptors initiating PPE and the theory that selective 5-HT2B antagonists might be effective prophylactic therapies for migraine.

Glomerular and tubular interactions between renal adrenergic activity and nitric oxide

1995 ◽  
Vol 268 (6) ◽  
pp. F1004-F1008 ◽  
Author(s):  
F. B. Gabbai ◽  
S. C. Thomson ◽  
O. Peterson ◽  
L. Wead ◽  
K. Malvey ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Glomerular Filtration ◽  
Renal Nerves ◽  
Ang Ii ◽  
Nitric Oxide Synthase Inhibitor ◽  
Adrenergic Activity ◽  
Single Nephron ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Endothelium-dependent nitric oxide (EDNO) exerts control over the processes of glomerular filtration and tubular reabsorption. The importance of the renal nerves to the tonic influence of EDNO in the glomerular microcirculation and proximal tubule was tested by renal micropuncture in euvolemic adult male Munich-Wistar rats. The physical determinants of glomerular filtration and proximal reabsorption were assessed before and during administration of the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA), in control animals and in animals 5–9 days after either ipsilateral surgical renal denervation (DNX) or after either sham surgery (SHX). L-NMMA caused single-nephron glomerular filtration rate to decline in control and SHX animals but not in DNX rats. L-NMMA caused a reduction in proximal reabsorption in control and SHX rats, which was prevented by prior DNX. DNX did not alter urinary guanosine 3',5'-cyclic monophosphate excretion, and, although DNX upregulates glomerular angiotensin II (ANG II) receptors, prior DNX did not alter intrarenal ANG II content as evaluated by radioimmunoassay. Some component of renal adrenergic activity is required for the full expression of the glomerular and tubular effects of blockade of nitric oxide synthase.

Effects of Early Neuronal and Delayed Inducible Nitric Oxide Synthase Blockade on Cardiovascular, Renal, and Hepatic Function in Ovine Sepsis

2010 ◽  
Vol 113 (6) ◽  
pp. 1376-1384 ◽  
Author(s):  
Matthias Lange ◽  
Atsumori Hamahata ◽  
Daniel L. Traber ◽  
Yoshimitsu Nakano ◽  
Aimalohi Esechie ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Nitric Oxide Synthase Inhibitor ◽  
Nitrite Nitrate ◽  
Synthase Inhibitor ◽  
Plasma Nitrite ◽  
Oxide Synthase ◽  
Organ Dysfunctions ◽  
Inducible Nitric Oxide

Background Recent evidence suggests that nitric oxide produced via the neuronal nitric oxide synthase is involved mainly in the early response to sepsis, whereas nitric oxide derived from the inducible nitric oxide synthase is responsible during the later phase. We hypothesized that early neuronal and delayed inducible nitric oxide synthase blockade attenuates multiple organ dysfunctions during sepsis. Methods Sheep were randomly allocated to sham-injured, nontreated animals (n = 6); injured (48 breaths of cotton smoke and instillation of Pseudomonas aeruginosa into the lungs), nontreated animals (n = 7); and injured animals treated with a neuronal nitric oxide synthase inhibitor from 1 to 12 h and an inducible nitric oxide synthase inhibitor from 12 to 24 h postinjury (n = 6). Results The injury induced arterial hypotension, vascular leakage, myocardial depression, and signs of renal and hepatic dysfunctions. The treatment significantly attenuated, but did not fully prevent, the decreases in mean arterial pressure and left ventricular stroke work index. Although the elevation of creatinine levels was partially prevented, the decreases in urine output and creatinine clearance were not affected. The injury-related increases in bilirubin levels, international normalized ratio, and lipid peroxidation in liver tissue were significantly attenuated. Although plasma nitrite/nitrate levels were significantly increased versus baseline from 12-24 h in controls, plasma nitrite/nitrate levels were not increased in treated animals. Conclusions The combination treatment shows potential benefit on sepsis-related arterial hypotension and surrogate parameters of organ dysfunctions in sheep. It may be crucial to identify the time course of expression and activation of different nitric oxide synthase isoforms in future investigations.

Myogenic reactivity is reduced in small renal arteries isolated from relaxin-treated rats

2002 ◽  
Vol 283 (2) ◽  
pp. R349-R355 ◽  
Author(s):  
Jacqueline Novak ◽  
Rolando J. J. Ramirez ◽  
Robin E. Gandley ◽  
O. David Sherwood ◽  
Kirk P. Conrad
Keyword(s):  
Nitric Oxide ◽  
Virgin Female ◽  
Renal Arteries ◽  
Mesenteric Arteries ◽  
Blood Levels ◽  
Renal Circulation ◽  
Nitric Oxide Synthase Inhibitor ◽  
Myogenic Responses ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Administration of the ovarian hormone relaxin to nonpregnant rats vasodilates the renal circulation comparable to pregnancy. This vasodilation is mediated by endothelin (ET), the ETB receptor, and nitric oxide. Furthermore, endogenous relaxin mediates the renal vasodilation and hyperfiltration that occur during gestation. The goal of this study was to investigate whether myogenic reactivity of small renal and mesenteric arteries is reduced in relaxin-treated rats comparable to the pregnant condition. Relaxin or vehicle was administered to virgin female Long-Evans rats for 5 days at 4 μg/h, thereby producing midgestational blood levels of the hormone. The myogenic responses of small renal arteries (200–300 μm in diameter) isolated from these animals were evaluated in an isobaric arteriograph system. Myogenic reactivity was significantly reduced in the small renal arteries from relaxin-treated compared with vehicle-treated rats. The reduced myogenic responses were mediated by the ETB receptor and nitric oxide since the selective ETB receptor antagonist RES-701–1 and the nitric oxide synthase inhibitor N G-nitro-l-arginine methyl ester restored myogenic reactivity to virgin levels. The influence of relaxin was not limited to the renal circulation because myogenic reactivity was also reduced in small mesenteric arteries isolated from relaxin-treated rats. Thus relaxin administration to nonpregnant rats mimics pregnancy, insofar as myogenic reactivity of small renal and mesenteric arteries is reduced in both conditions.

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