Segmental heterogeneity of NO-mediated pulmonary vasodilation in rats

1994 ◽  
Vol 267 (2) ◽  
pp. H494-H499 ◽  
Author(s):  
M. R. Eichinger ◽  
B. R. Walker
Keyword(s):  
Sodium Nitroprusside ◽  
Arginine Vasopressin ◽  
Calcium Ionophore ◽  
Vascular Occlusion ◽  
Physiological Saline ◽  
Calcium Ionophore A23187 ◽  
Pulmonary Vasculature ◽  
Ionophore A23187 ◽  
Sprague Dawley ◽  
No Donor

Nitric oxide (NO) is known to elicit vasodilation in the preconstricted rat lung. However, the sites of dilation within the pulmonary vasculature remain unknown. We hypothesized that donated NO would dilate all areas of constriction within the pulmonary vasculature, whereas receptor-mediated, NO-induced dilations would correspond to regional binding of agents. Isolated lungs from male Sprague-Dawley rats were perfused at constant flow with physiological saline solution. Pulmonary arterial and pulmonary venous pressures were monitored, while pulmonary microvascular pressures were estimated by vascular occlusion. Lungs were constricted with U-46619, and upon development of a stable degree of vasoconstriction, the NO donor sodium nitroprusside or the endothelium-dependent dilators A23187, arginine vasopressin, or ATP were administered. U-46619 caused constriction of both arterial and venous segments. Administration of sodium nitroprusside and the calcium ionophore A23187 elicited similar dilation of preconstricted arterial and venous segments. Arginine vasopressin significantly dilated both arterial and venous segments, with a greater reversal of venous resistance. In contrast, ATP significantly reduced arterial resistance more than venous. These results demonstrate that donated NO uniformly dilates all constricted regions of the pulmonary vasculature. However, receptor-mediated, endothelium-dependent dilators display characteristic heterogeneities in the sites of decreased pulmonary vascular resistance.

Maintained endothelium-dependent pulmonary vasodilation following chronic hypoxia in the rat

1993 ◽  
Vol 74 (1) ◽  
pp. 339-344 ◽  
Author(s):  
R. D. Russ ◽  
B. R. Walker
Keyword(s):  
Perfusion Pressure ◽  
Calcium Ionophore ◽  
Barometric Pressure ◽  
Calcium Ionophore A23187 ◽  
Pulmonary Vasculature ◽  
Hypoxic Exposure ◽  
Ionophore A23187 ◽  
Sprague Dawley ◽  
Pulmonary Vasodilation ◽  
Sprague Dawley Rats

We have previously demonstrated that arginine vasopressin (AVP) dilates the preconstricted pulmonary vasculature via the release of nitric oxide (NO). However, recent evidence suggests that NO release in response to other agents may be suppressed in lungs from animals that have been chronically exposed to hypoxia. The purpose of the present experiment was to determine whether vasopressinergic pulmonary vasodilation is similarly affected by chronic exposure to hypoxia (barometric pressure = 380 Torr for 4 wk). Inhibition of NO synthesis with N omega-nitro-L-arginine (L-NNA) had no effect on baseline perfusion pressure in isolated salt-perfused lungs from either control or chronically hypoxic rats. Similarly, pulmonary vasodilatory responses to AVP and the calcium ionophore A23187 were unaffected by chronic hypoxic exposure. Pretreatment with the cyclooxygenase inhibitor meclofenamate did not alter vasopressinergic pulmonary vasodilation in lungs from either control or chronically hypoxic animals, ruling out involvement of vasodilator prostaglandins in the response to AVP. In contrast, vasodilatory responses to both AVP and A23187 were inhibited by L-NNA pretreatment not only in lungs from control animals but also in lungs from chronically hypoxic rats, suggesting the involvement of NO in the vasodilatory response. The inhibition by L-NNA was reversible by prior addition of excess L-arginine but not by D-arginine. In addition, vasodilatory responses to the endothelium-independent vasodilators sodium nitroprusside and isoproterenol were unaffected by chronic hypoxic exposure. We conclude that endothelium-dependent vasodilation remains intact in male Sprague-Dawley rats after chronic hypoxic exposure.

Endothelial modulation of porcine coronary microcirculation perfused via immature collaterals

1992 ◽  
Vol 262 (6) ◽  
pp. H1669-H1675 ◽  
Author(s):  
F. W. Sellke ◽  
Y. Kagaya ◽  
R. G. Johnson ◽  
T. Shafique ◽  
F. J. Schoen ◽  
...  
Keyword(s):  
Sodium Nitroprusside ◽  
Calcium Ionophore ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Flow State ◽  
Vascular Studies ◽  
Collateral Vessels ◽  
Endothelium Dependent Relaxation ◽  
Minimal Evidence ◽  
Dependent Agents

Porcine hearts have relatively few native collateral vessels and lack the propensity to develop normal perfusion to the collateral-dependent myocardium. To examine microvascular responses in the collateral-dependent region, collateral vessels were stimulated in pigs by the Ameroid constrictor technique. After 4–7 wk, isolated microarterial vessels (90–170 microns ID) were studied in a pressurized (40 mmHg), no-flow state. Microvessels from noninstrumented pigs were used as controls for vascular studies. Although myocardium in the collateral-dependent region showed minimal evidence of infarction, percent systolic shortening was reduced at rest and after pacing compared with myocardium in the normally perfused region. Relaxations to the receptor-mediated endothelium-dependent agents ADP and bradykinin were impaired in collateral-dependent coronary microvessels. Relaxations to the calcium ionophore A23187, which acts through a non-receptor-mediated mechanism, were similar in control and Ameroid microvessels. Relaxations to the endothelium-independent agent sodium nitroprusside were markedly enhanced in microvessels from the collateral-dependent region compared with microvessels from control hearts. In conclusion, receptor-mediated endothelium-dependent relaxation is impaired and endothelium-independent relaxation to sodium nitroprusside is enhanced in microvessels from myocardium perfused by immature collateral vessels.

scholarly journals Linolenic Acid Attenuates the Vasodilation Induced by Acetylcholine in Isolated Rat Aortae

Dose-Response ◽  
2019 ◽  
Vol 17 (4) ◽  
pp. 155932581989414 ◽  
Author(s):  
Soo Hee Lee ◽  
Seong-Ho Ok ◽  
Ji-Yoon Kim ◽  
Raghavendra Baregundi Subbarao ◽  
Sung Il Bae ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Linolenic Acid ◽  
Calcium Ionophore ◽  
Underlying Mechanism ◽  
Cyclic Guanosine Monophosphate ◽  
Calcium Ionophore A23187 ◽  
Guanosine Monophosphate ◽  
Ionophore A23187 ◽  
Isolated Rat

This study aims to examine the effect of linolenic acid on the vasodilation or vasoconstriction induced by acetylcholine and bupivacaine in isolated rat aortae and its underlying mechanism. The effect of linolenic acid on the vasodilation induced by acetylcholine, the calcium ionophore A23187, sodium nitroprusside, and 8-bromoguanosine 3′,5′-cyclic monophosphate sodium salt (bromo-cyclic guanosine monophosphate [bromo-cGMP]) in endothelium-intact and endothelium-denuded aortae was examined. Linolenic acid inhibited vasodilation induced by acetylcholine, calcium ionophore A23187, and sodium nitroprusside. However, this fatty acid increased bromo-cGMP-induced vasodilation in endothelium-denuded aortae. Linolenic acid increased bupivacaine-induced contraction in endothelium-intact aortae, whereas it decreased bupivacaine-induced contraction in endothelium-intact aortae with Nω-nitro-l-arginine methyl ester and endothelium-denuded aortae. Linolenic acid inhibited acetylcholine- and bupivacaine-induced phosphorylation of endothelial nitric oxide synthase. Sodium nitroprusside increased cGMP in endothelium-denuded aortic strips, whereas bupivacaine decreased cGMP in endothelium-intact aortic strips. Linolenic acid decreased cGMP levels produced by bupivacaine and sodium nitroprusside. Together, these results suggest that linolenic acid inhibits acetylcholine-induced relaxation by inhibiting a step just prior to nitric oxide-induced cGMP formation. In addition, linolenic acid-mediated inhibition of vasodilation induced by a toxic concentration (3 × 10−4 M) of bupivacaine seems to be partially associated with inhibition of the nitric oxide–cGMP pathway.

Enhanced pulmonary arterial dilation to arginine vasopressin in chronically hypoxic rats

1994 ◽  
Vol 267 (6) ◽  
pp. H2413-H2419 ◽  
Author(s):  
M. R. Eichinger ◽  
B. R. Walker
Keyword(s):  
Sodium Nitroprusside ◽  
Arginine Vasopressin ◽  
Chronic Hypoxia ◽  
Pressor Response ◽  
Hypoxic Exposure ◽  
Sprague Dawley ◽  
No Donor ◽  
A 23187 ◽  
Pulmonary Arterial ◽  
Arterial Dilation

Chronic hypoxic exposure elicits pulmonary vascular remodeling and may alter normal pulmonary endothelial function. We examined the vasodilatory response to the receptor-mediated endothelium-dependent dilator arginine vasopressin (AVP), the non-receptor-mediated endothelium-dependent dilator A-23187, and the nitric oxide (NO) donor sodium nitroprusside in lungs isolated from control or chronically hypoxic rats. Lungs were isolated from male Sprague-Dawley rats and perfused with a physiological saline solution containing 4% albumin. Arterial and venous pressures were monitored and microvascular pressure was estimated by double occlusion, allowing assessment of segmental resistances. After equilibration, lungs were constricted with the thromboxane mimetic U-46619. Upon development of a stable pressor response, lungs were dilated with one of the above agents. A series of doses of AVP was administered to separate groups of lungs from control or chronically hypoxic rats. Lungs from chronically hypoxic rats exhibited an augmented dilatory response to AVP compared with control lungs, and this effect was due to enhanced dilation of precapillary segments. The total and segmental vasodilatory responses to A-23187 and sodium nitroprusside were not different between the two groups of lungs, suggesting that chronic hypoxia did not upregulate the enzyme NO synthase or enhance the vascular smooth muscle responsiveness to NO. Thus our data suggest that the augmented total and pulmonary arterial dilation to AVP after chronic hypoxia is most likely due to altered receptor-mediated processes of the hormone.

Endothelial dysfunction is induced by proinflammatory oxidant hypochlorous acid

2001 ◽  
Vol 281 (4) ◽  
pp. H1469-H1475 ◽  
Author(s):  
Chunxiang Zhang ◽  
Rakesh Patel ◽  
Jason P. Eiserich ◽  
Fen Zhou ◽  
Stacey Kelpke ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Hypochlorous Acid ◽  
Tissue Injury ◽  
Calcium Ionophore ◽  
Aortic Ring ◽  
Inhibitory Effect ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Sprague Dawley ◽  
Inflammatory Conditions

The myeloperoxidase (MPO)-derived oxidant hypochlorous acid (HOCl) plays a role in tissue injury under inflammatory conditions. The present study tests the hypothesis that HOCl decreases nitric oxide (NO) bioavailability in the vasculature of Sprague-Dawley rats. Aortic ring segments were pretreated with HOCl (1–50 μM) followed by extensive washing. Endothelium-dependent relaxation was then assessed by cumulative addition of acetylcholine (ACh) or the calcium ionophore A23187 . HOCl treatment significantly impaired both ACh- and A23187 -mediated relaxation. In contrast, endothelium-independent relaxation induced by sodium nitroprusside was unaffected. The inhibitory effect of HOCl on ACh-induced relaxation was reversed by exposure of ring segments to l-arginine but notd-arginine. In cellular studies, HOCl did not alter endothelial NO synthase (NOS III) protein or activity, but inhibited formation of the NO metabolites nitrate (NO[Formula: see text]) and nitrite (NO[Formula: see text]). The reduction in total NO metabolite production in bovine aortic endothelial cells was also reversed by addition of l-arginine. These data suggest that HOCl induces endothelial dysfunction via modification ofl-arginine.

Agonist-induced isotonic contraction of cultured mesangial cells after multiple passage

1985 ◽  
Vol 249 (1) ◽  
pp. C48-C55 ◽  
Author(s):  
M. A. Venkatachalam ◽  
J. I. Kreisberg
Keyword(s):  
Arginine Vasopressin ◽  
Mesangial Cells ◽  
Calcium Ionophore ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Hydroxyethyl Methacrylate ◽  
Isotonic Contraction ◽  
Substrate Adhesion ◽  
Usual Manner ◽  
Prolonged Culture

Contractile cells under conditions of prolonged culture lose their ability to contract in the usual manner (i.e., isotonically). One explanation for this may be that contraction is prevented by tight cell-to-substrate adhesion. Two models in which substrate adhesiveness was expected to be diminished were used to test this hypothesis. In one, cells were seeded onto collagen-coated dishes and used within 40 min of plating. In the other, cells were plated onto dishes coated with poly-2-hydroxyethyl methacrylate (poly-HEMA) and used, depending on thickness of the poly-HEMA substrate, up to periods of 1 wk. Cells plated onto such substrates contracted when challenged with either PGE2 (2 X 10(-6) and 2 X 10(-9) M), arginine vasopressin (AVP, 10(-6)-10(-9) ), or the calcium ionophore A23187 (5 micrograms/ml). Contraction took place within 5-15 min at 37 degrees C. The contraction seen with AVP was due to its pressor action because 1-desamino-8-D-arginine vasopressin (dDAVP), the antidiuretic analogue, did not cause contraction and the anti-pressor analogue [1-(beta-mercapto-beta beta-cyclopentamethylene propionic acid)-4-valine 8-D-arginine]-vasopressin [d(CH2)5-VDAVP] blocked contraction by AVP. The contraction seen with AVP was dependent on extracellular calcium, whereas that observed with prostaglandin E2 (PGE2) was not.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Endothelial Dysfunction in Cerebral Vessels following Carotid Artery Infusion of Phorbol Ester in Rabbits: The Role of Polymorphonuclear Leukocytes

1994 ◽  
Vol 14 (6) ◽  
pp. 1078-1087 ◽  
Author(s):  
S. E. Akopov ◽  
R. Sercombe ◽  
J. Seylaz
Keyword(s):  
Endothelial Dysfunction ◽  
Carotid Artery ◽  
Sodium Nitroprusside ◽  
Calcium Ionophore ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Significant Difference ◽  
Left And Right ◽  
Endothelium Dependent Relaxation

The effect of 4β-phorbol-12β-myristate-13α-acetate (PMA) on endothelium-dependent and endothelium-independent vasoconstriction and vasodilation was studied in isolated segments of rabbit middle cerebral artery (MCA). Concentration-dependent responses of the left and right MCA to the constrictors KCl, noradrenaline, uridine 5′-triphosphate, serotonin, and histamine, as well as to the dilators acetylcholine, bradykinin, sodium nitroprusside, and calcium ionophore (A23187), were compared in control animals and after PMA injection into the left common carotid artery. In the control animals there was no significant difference in the responses of the left and right MCA to either the constrictors or the dilators studied. After PMA injection the endothelium-dependent relaxation in response to acetylcholine, bradykinin, and A23187 was reduced in the left MCA (PMA-injected side), whereas the effect of the endothelium-independent dilator sodium nitroprusside remained unchanged. Simultaneously greater contractile responses of the left MCA to serotonin and histamine were obtained. Neither infusion of l-arginine in vivo before the PMA injection nor incubation of the isolated MCA segments with l-arginine affected this difference in MCA reactivity. Platelet depletion did not change the PMA-induced reduction in the endothelium-dependent relaxation, whereas after leukocyte depletion this reduction practically disappeared. These results suggest that the PMA-induced brain microembolia causes acute endothelial dysfunction, which is possibly mediated by intravascular activation of leukocytes and is independent of nitric oxide synthesis from l-arginine. This phenomenon might play an important role in cerebral angiospastic disorders after intravascular activation of leukocytes in cerebral ischemia and reperfusion.

scholarly journals Lipid Emulsion Attenuates Acetylcholine-Induced Relaxation in Isolated Rat Aorta

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Seong-Ho Ok ◽  
Soo Hee Lee ◽  
Jongsun Yu ◽  
Jungchul Park ◽  
Il-Woo Shin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Lipid Emulsion ◽  
Umbilical Vein ◽  
Calcium Ionophore ◽  
Rat Aorta ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Enos Phosphorylation ◽  
Isolated Rat

We investigated the effect of Lipofundin MCT/LCT and Intralipid on acetylcholine-induced nitric oxide- (NO-) mediated relaxation in rat aorta to determine which lipid emulsion (LE) is more potent in terms of inhibition of NO-induced relaxation. Dose-response curves of responses induced by acetylcholine, the calcium ionophore A23187, and sodium nitroprusside were generated using isolated rat aorta with or without LE. The effect of Lipofundin MCT/LCT on acetylcholine-induced endothelial nitric oxide synthase (eNOS) phosphorylation in human umbilical vein endothelial cells (HUVECs) was investigated using western blotting. Lipofundin MCT/LCT (0.1 and 0.2%) attenuated acetylcholine-induced relaxation in endothelium-intact aorta with or without tiron, whereas 0.2% Intralipid only inhibited relaxation. Lipofundin MCT/LCT inhibited relaxation induced by the calcium ionophore A23187 and sodium nitroprusside in endothelium-intact aorta, but Lipofundin MCT/LCT had no effect on sodium nitroprusside-induced relaxation in the endothelium-denuded aorta. Combined pretreatment withl-arginine plus Lipofundin MCT/LCT increased acetylcholine-induced maximal relaxation in endothelium-intact aorta compared with Lipofundin MCT/LCT alone.l-Arginine attenuated Lipofundin MCT/LCT-mediated inhibition of acetylcholine-induced eNOS phosphorylation in HUVECs. Taken together, Lipofundin MCT/LCT attenuated acetylcholine-induced NO-mediated relaxation via an inhibitory effect on the endothelium including eNOS, which is proximal to activation of guanylyl cyclase.

Dissociation between endothelium-dependent relaxations and increases in cGMP in systemic veins

1991 ◽  
Vol 260 (5) ◽  
pp. H1531-H1537 ◽  
Author(s):  
M. Vidal ◽  
P. M. Vanhoutte ◽  
V. M. Miller
Keyword(s):  
Methylene Blue ◽  
Smooth Muscle ◽  
Sodium Nitroprusside ◽  
Soluble Guanylate Cyclase ◽  
Isometric Force ◽  
Calcium Ionophore ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Femoral Arteries ◽  
Arteries And Veins

In canine systemic veins, in contrast to what is observed in mammalian systemic arteries, endothelium-dependent relaxations to the calcium ionophore A23187 are not diminished by the inhibitor of soluble guanylate cyclase, methylene blue. Therefore, experiments were designed to determine whether these relaxations in the veins are associated with the accumulation of guanosine 3',5'-cyclic monophosphate (cGMP). Rings of canine femoral arteries and veins with and without endothelium were suspended for the measurement of isometric force in organ chambers; cGMP was measured by radioimmunoassay. In arteries and veins contracted with norepinephrine, the tissue content of cGMP was greater in rings with than without endothelium. This difference was decreased by methylene blue (10(-5) M). A23187 (3 X 10(-7) M, for 1 min) increased the accumulation of cGMP, which was temporally related with the onset of relaxation in tissues with endothelium. Methylene blue inhibited the accumulation of cGMP in both blood vessels but inhibited the relaxations only in the arteries. In rings without endothelium, sodium nitroprusside (3 X 10(-7) and 10(-5) M) initiated increases in cGMP, which followed the onset of relaxation. Neither response to sodium nitroprusside was reduced by methylene blue. These results suggest that in canine femoral arteries and veins, relaxation of the smooth muscle to sodium nitroprusside are mediated by a mechanism distinct from changes in cGMP. Likewise, in canine systemic veins, endothelium-derived factor(s) released in response to A23187 also can initiate relaxation of the smooth muscle by a mechanism distinct from changes in cGMP.

Sign in / Sign up

Export Citation Format

Share Document