Impairment of endothelium-dependent relaxation of superior mesenteric artery in genetically diabetic WBN/Kob rats

1993 ◽  
Vol 71 (3-4) ◽  
pp. 297-300 ◽  
Author(s):  
Noriyuki Miyata ◽  
Hiroko Yamaura ◽  
Katsuharu Tsuchida ◽  
Shigeru Okuyama ◽  
Susumu Otomo ◽  
...  
Keyword(s):  
Sodium Nitroprusside ◽  
Superior Mesenteric Artery ◽  
Mesenteric Artery ◽  
Wistar Rats ◽  
Diabetic Rats ◽  
Mesenteric Arteries ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor ◽  
Relaxation Responses ◽  
Endothelium Dependent Relaxation

The endothelium-dependent relaxation of superior mesenteric arteries of Wistar and genetically diabetic WBN/Kob rats was compared. Endothelium-dependent relaxation induced by acetylcholine (ACh) and A23187 was depressed in WBN/Kob rats. Relaxation induced by sodium nitroprusside, an endothelium-independent agent, in strips from WBN/Kob rats was similar to that in strips from Wistar rats. Indomethacin (5 × 10−6 M) enhanced the relaxation responses to ACh in strips from both WBN/Kob and Wistar rats; however, endothelium-dependent relaxation induced by ACh remained attenuated in WBN/Kob rats. These results show that endothelium-dependent relaxation is impaired not only in thoracic aorta but also in superior mesenteric arteries in genetically diabetic rats.Key words: acetylcholine, A23187, sodium nitroprusside, indomethacin, genetically diabetic rats, endothelium-derived relaxing factor.

Age-related changes in endothelium-dependent relaxation in aorta from genetically diabetic WBN/Kob rats

1992 ◽  
Vol 262 (4) ◽  
pp. H1104-H1109 ◽  
Author(s):  
N. Miyata ◽  
K. Tsuchida ◽  
S. Okuyama ◽  
S. Otomo ◽  
K. Kamata ◽  
...  
Keyword(s):  
Sodium Nitroprusside ◽  
Matched Control ◽  
Vascular Complications ◽  
Diabetic Rats ◽  
Response Curves ◽  
Functional Changes ◽  
Age Related ◽  
Relaxation Responses ◽  
Effects Of Aging ◽  
Endothelium Dependent Relaxation

Experiments were designed to investigate the effects of aging and hyperglycemia on relaxation of the aorta for both endothelium-dependent and -independent agents in Wistar (control) and WBN/Kob (genetically diabetic) rats. The concentration of glucose in serum was elevated significantly in aged (90-92 wk) but not young (13-15 wk) WBN/Kob rats. Endothelium-dependent relaxations of both control and WBN/Kob rats to acetylcholine were reduced by aging. The relaxations induced by acetylcholine in aortic strips were significantly attenuated in both young (nondiabetic) and aged (diabetic) WBN/Kob rats, compared with those from age-matched control vessels, respectively. The concentration-response curves for sodium nitroprusside in aortic strips from both aged control and aged WBN/Kob rats were shifted to the left when compared with those from young rats, respectively. However, the maximal relaxation responses to sodium nitroprusside showed no difference among all vessels studied. The relaxations induced by sodium nitroprusside in aortic strips from both young and aged WBN/Kob rats were similar to those from age-matched control rats, respectively. The relaxations induced by atrial natriuretic peptide showed no difference among all vessels studied. In genetically diabetic rats, functional changes in endothelium occurred before elevation of the levels of glucose in the serum. Thus impaired endothelium-dependent relaxation may play an important role in the high incidence of vascular complications in diabetes mellitus.

Oxygen modulates endothelium-derived relaxing factor production in fetal pulmonary arteries

1992 ◽  
Vol 262 (2) ◽  
pp. H355-H364 ◽  
Author(s):  
P. W. Shaul ◽  
M. A. Farrar ◽  
T. M. Zellers
Keyword(s):  
Oxygen Tension ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Pulmonary Arteries ◽  
Mesenteric Arteries ◽  
Cgmp Production ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor ◽  
Ovine Fetal ◽  
Endothelium Dependent Relaxation

Alterations in endothelium-derived relaxing factor (EDRF) production or mechanism of action may be involved in the responses of the developing pulmonary vasculature to changes in oxygenation. In this study the effects of acute changes in in vitro oxygen tension on EDRF production were determined in isolated segments of ovine fetal intrapulmonary arteries (4th generation) obtained at 125-135 days of gestation (term 144 +/- 4 days). EDRF production was assessed by measuring segment guanosine 3',5'-cyclic monophosphate (cGMP) accumulation in the presence of a phosphodiesterase inhibitor. Basal (nonstimulated) cGMP production and cGMP production with acetylcholine (ACh) stimulation were dependent on the presence of the endothelium, on the availability of L-arginine, and on soluble guanylate cyclase activity, confirming that they were indicative of EDRF production. cGMP production with sodium nitroprusside (SNP) was used to discriminate changes in the sensitivity of soluble guanylate cyclase with varying conditions. With decreasing oxygen tension, basal and ACh-stimulated cGMP production were attenuated, whereas cGMP production with SNP was not, indicating oxygen modulation of EDRF production. Studies of endothelium-dependent relaxation yielded comparable findings in that the response to ACh was attenuated, but that to SNP was not altered by decreased oxygenation. In addition, the decline in endothelium-dependent relaxation with decreased oxygen tension was rapidly reversed when oxygenation was increased. Parallel experiments examining cGMP production in similarly sized mesenteric arteries revealed that the effect of oxygen on pulmonary artery EDRF production may be specific to that vascular bed. These findings indicate that oxygen selectively modulates EDRF production and endothelium-dependent relaxation in ovine fetal pulmonary arteries. Direct effects of oxygen on EDRF production may at least partially underlie the responses of the developing pulmonary circulation to changes in oxygenation.

Selective Impairment of Acetylcholine-Mediated Endothelium-Dependent Relaxation in Isolated Resistance Arteries of the Streptozotocin-Induced Diabetic Rat

1995 ◽  
Vol 88 (5) ◽  
pp. 519-524 ◽  
Author(s):  
P. D. Taylor ◽  
J. E. Graves ◽  
L. Poston
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Vascular Complications ◽  
Signal Transduction Pathway ◽  
Diabetic Rats ◽  
Mesenteric Arteries ◽  
Diabetic Rat ◽  
Resistance Arteries ◽  
Significant Difference ◽  
Endothelium Dependent Relaxation

1. There is growing evidence that an impairment in the function of nitric oxide synthase may play a role in the vascular complications of diabetes mellitus. The relaxation of resistance arteries from the mesenteric and hindlimb circulations of streptozotocin-induced diabetic rats and age-matched controls were investigated using two endothelium-dependent vasodilators, bradykinin and acetylcholine, and the endothelium-independent vasodilator sodium nitroprusside. The contractile responses to the α1-adrenergic agonist phenylephrine were also studied. 2. Endothelium-dependent relaxation to acetylcholine was impaired in the diabetic rats in arteries from both mesenteric and hindlimb circulations (hindlimb pEC50, 7.93 ± 0.08 in the control compared with 7.38 ± 0.10 in the diabetic rat; mesenteric pEC50, 7.47 ± 0.04 in the control compared with 6.65 ± 0.06 in the diabetic rat; unpaired t-test P < 0.0001). Bradykinin elicited relaxation in only the mesenteric arteries, and this was not attenuated in the diabetic rats compared with controls. 3. Endothelium-independent relaxation to sodium nitroprusside was similar in the two circulations and was not abnormal in the diabetic rats. There was no significant difference in constrictor responses to phenylephrine between diabetic rats and controls in either the hindlimb or mesenteric arteries, in contrast to an earlier study in which we showed increased sensitivity to noradrenaline. 4. The diabetic rats therefore demonstrated a specific impairment of receptor-mediated endothelium-dependent relaxation to acetylcholine. These results suggest that, in this diabetic model, the ability of the endothelium to relax arteries via nitric oxide may involve a defect of a specific signal transduction pathway, leading to reduced production of nitric oxide.

Alterations in EDHF-type relaxation and phosphodiesterase activity in mesenteric arteries from diabetic rats

2003 ◽  
Vol 285 (1) ◽  
pp. H283-H291 ◽  
Author(s):  
Takayuki Matsumoto ◽  
Tsuneo Kobayashi ◽  
Katsuo Kamata
Keyword(s):  
Gap Junctions ◽  
Superior Mesenteric Artery ◽  
Mesenteric Artery ◽  
Matched Control ◽  
Diabetic Rats ◽  
Selective Inhibitor ◽  
Mesenteric Arteries ◽  
Phosphodiesterase Activity ◽  
Camp Phosphodiesterase

In isolated superior mesenteric artery rings from age-matched control rats and streptozotocin (STZ)-induced diabetic rats, we investigated the role of cAMP in endothelium-derived hyperpolarizing factor (EDHF)-type relaxation. The ACh-induced EDHF-type relaxation was significantly weaker in STZ-induced diabetic rats than in control rats, and in both groups of rats it was attenuated by 18α-glycyrrhetinic acid (18α-GA), an inhibitor of gap junctions, and enhanced by IBMX, a cAMP-phosphodiesterase (PDE) inhibitor. These enhanced EDHF-type responses were very similar in magnitude between diabetic and age-matched control rats. The EDHF-type relaxation was enhanced by cilostamide, a PDE3-selective inhibitor, but not by Ro 20–1724, a PDE4-selective inhibitor. The expression levels of the mRNAs and proteins for two cAMP PDEs (PDE3A, PDE3B) were significantly increased in STZ-induced diabetic rats, but those for PDE4D were not. We conclude that the impairment of EDHF-type relaxations in STZ-induced diabetic rats may be attributed to a reduction in the action of cAMP via increased PDE activity.

Endothelium derived relaxing factor release from canine coronary artery by leukocytes

1995 ◽  
Vol 73 (3) ◽  
pp. 404-408 ◽  
Author(s):  
Joseph F. Kleha ◽  
Pierre Devesly ◽  
Anthony Johns
Keyword(s):  
Endothelial Cell ◽  
Coronary Artery ◽  
Human Monocyte ◽  
Relaxing Factor ◽  
Canine Coronary Artery ◽  
Endothelium Derived Relaxing Factor ◽  
Ly 83583 ◽  
Muscle Calcium ◽  
Endothelium Dependent Relaxation ◽  
Factor Release

Lectins, known to recognize endothelial cell adhesion molecules, have been shown to release endothelium-derived relaxing factor (EDRF) from blood vessels. We investigated the effects of different leukocyte-type cells to determine if these cells, by interacting with the endothelium, could release EDRF from the circumflex branch of the canine coronary artery. The following cells were investigated: human promyelocytic leukemia (HL-60), human monocyte (THP-1), and human Burkitt lymphoma (DAUDI). All of these cells produced a significant endothelium-dependent relaxation of the dog coronary artery in the presence of ibuprofen. The endothelium-dependent relaxations were reversed by hemoglobin (10 μM), methylene blue (3 μM), 6-anilino-5,8-quinolinedione (LY 83583, 30 μM), and NG-nitro-L-arginine methyl ester (L-NAME, 1 mM). HL-60 cells grown in the presence of 1 mM L-NAME retained their ability to cause endothelium-dependent relaxation of the canine coronary artery, suggesting that the source of the NO was the endothelium and not the HL-60 cells. The cell-induced vascular relaxation could be obtained in the absence of extracellular calcium. It is suggested that HL-60, THP-1, and DAUDI cells interact with a specific receptor on the endothelial cell and as a result of this interaction the endothelial cells are stimulated to release EDRF.Key words: endothelium-derived relaxing factor, nitric oxide, endothelium, HL-60, DAUDI, THP-1, smooth muscle, calcium, contraction, canine coronary artery.

Functional changes in adenylyl cyclases and associated decreases in relaxation responses in mesenteric arteries from diabetic rats

2005 ◽  
Vol 289 (5) ◽  
pp. H2234-H2243 ◽  
Author(s):  
Takayuki Matsumoto ◽  
Kentaro Wakabayashi ◽  
Tsuneo Kobayashi ◽  
Katsuo Kamata
Keyword(s):  
Mesenteric Artery ◽  
Diabetic Rats ◽  
Functional Change ◽  
Water Soluble ◽  
Mesenteric Arteries ◽  
Diabetic Rat ◽  
Adenylyl Cyclases ◽  
Camp Production ◽  
Functional Changes ◽  
Rat Mesenteric Artery

To assess the functional change in adenylyl cyclases (AC) associated with the diabetic state, we investigated AC-mediated relaxations and cAMP production in mesenteric arteries from rats with streptozotocin (STZ)-induced diabetes. The relaxations induced by the water-soluble forskolin (FSK) analog NKH477, which is a putative AC5 activator, but not by the β-adrenoceptor agonist isoproterenol (Iso) and the AC activator FSK, were reduced in intact diabetic mesenteric artery. In diabetic rats, however, Iso-, FSK-, and NKH477-induced relaxations were attenuated in the presence of inhibitors of nitric oxide synthase and cyclooxygenase. To exclude the influence of phosphodiesterase (PDE), we also examined the relaxations induced by several AC activators in the presence of 3-isobutyl-1-methylxanthine (IBMX; a PDE inhibitor). Under these conditions, the relaxation induced by Iso was greatly impaired in STZ-diabetic rats. This Iso-induced relaxation was significantly attenuated by pretreatment with SQ-22536, an AC inhibitor, in mesenteric rings from age-matched controls but not in those from STZ-diabetic rats. Under the same conditions, the relaxations induced by FSK or NKH477 were impaired in STZ-diabetic rats. Neither FSK- nor A-23187 (a Ca2+ ionophore)-induced cAMP production was significantly different between diabetics and controls. However, cAMP production induced by Iso or NKH477 was significantly impaired in diabetic mesenteric arteries. Expression of mRNAs and proteins for AC5/6 was lower in diabetic mesenteric arteries than in controls. These results suggest that AC-mediated relaxation is impaired in the STZ-diabetic rat mesenteric artery, perhaps reflecting a reduction in AC5/6 activity.

Is nitric oxide the only endothelium-derived relaxing factor in canine femoral veins?

1989 ◽  
Vol 257 (6) ◽  
pp. H1910-H1916 ◽  
Author(s):  
V. M. Miller ◽  
P. M. Vanhoutte
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Superoxide Dismutase ◽  
Sodium Nitroprusside ◽  
Femoral Vein ◽  
Pulmonary Veins ◽  
Chemical Properties ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor ◽  
Ly 83583

Nitric oxide may be an endothelium-derived relaxing factor in systemic arteries and pulmonary veins. The endothelium-derived relaxing factor of systemic veins has not been characterized. Experiments were designed to determine whether the endothelium-derived relaxing factor of systemic veins shared chemical properties and mechanisms of action with nitric oxide. Rings of the canine femoral vein with and without endothelium were suspended in organ chambers for the measurement of isometric force. In rings without endothelium, relaxations to nitric oxide were augmented by superoxide dismutase plus catalase and were inhibited by hemoglobin, methylene blue, and LY 83583. The endothelium-dependent relaxations to acetylcholine and A23187 were not augmented by superoxide dismutase plus catalase but were inhibited by hemoglobin and only moderately reduced by either methylene blue or LY 83583. Relaxations to sodium nitroprusside were not inhibited by methylene blue and LY 83583. Relaxations to sodium nitroprusside were inhibited by ouabain and K+-free solution; those to nitric oxide were not. These results indicate that although the endothelium-derived relaxing factor released from canine systemic veins shares some chemical properties with nitric oxide, the mechanism by which relaxations are induced by the two differ. A factor dissimilar to nitric oxide but acting like sodium nitroprusside may be released by the endothelium of canine systemic veins.

Comparison of acetylcholine-dependent relaxation in large and small arteries of rat mesenteric vascular bed

1994 ◽  
Vol 266 (3) ◽  
pp. H952-H958 ◽  
Author(s):  
J. J. Hwa ◽  
L. Ghibaudi ◽  
P. Williams ◽  
M. Chatterjee
Keyword(s):  
Methylene Blue ◽  
Channel Blocker ◽  
Mesenteric Arteries ◽  
K Channel ◽  
Resistance Arteries ◽  
Vascular Bed ◽  
Mesenteric Vascular Bed ◽  
Relaxation Responses ◽  
Endothelium Dependent Relaxation

The relative contributions of nitric oxide (NO) to in vitro relaxation responses elicited by acetylcholine (ACh) were compared in vessels of different sizes from the rat mesenteric vascular bed. ACh elicited an endothelium-dependent relaxation in phenylephrine-contracted superior mesenteric arteries (SMA, unstretched luminal diam 650 microns), which was blocked by compounds that inhibited NO, such as hemoglobin (10 microM), methylene blue (10 microM), and NG-monomethyl-L-arginine (1 mM). In contrast, the endothelium-dependent relaxation induced by ACh in phenylephrine-contracted mesenteric resistance arteries (MRA, unstretched luminal diam 200 microns) was not blocked by hemoglobin, methylene blue, or NG-monomethyl-L-arginine. KCl (25 mM) partially inhibited the ACh-dependent relaxation in MRA. Furthermore, the ACh-dependent relaxation in MRA was selectively inhibited by the Ca(2+)-activated K+ channel blocker charybdotoxin (0.1 microM). In contrast, the ATP-sensitive K+ channel blocker glibenclamide (50 microM) did not block the ACh-dependent relaxation in MRA. We conclude that 1) NO is a major component of the ACh-dependent relaxation in SMA and 2) the ACh-dependent relaxation of MRA is resistant to NO inhibitors but sensitive to a Ca(2+)-activated K+ channel blocker. This suggests that an endothelium-derived hyperpolarization factor may be involved in the relaxation of MRA.

Endothelium-dependent vasodilation of canine coronary collateral vessels

1991 ◽  
Vol 261 (6) ◽  
pp. H1797-H1801 ◽  
Author(s):  
N. M. Flynn ◽  
D. Kenny ◽  
L. R. Pelc ◽  
D. C. Warltier ◽  
Z. J. Bosnjak ◽  
...  
Keyword(s):  
Sodium Nitroprusside ◽  
Coronary Arteries ◽  
Maximal Response ◽  
Small Arteries ◽  
Relaxing Factor ◽  
Coronary Collateral ◽  
Prostaglandin F2 Alpha ◽  
Collateral Vessels ◽  
Endothelium Dependent Relaxation

The objective of this study was to determine whether endothelium-mediated relaxation occurs in canine coronary collateral vessels. Responses to endothelium-dependent vasodilators in coronary collateral vessels (250-350 microns) were compared with those obtained in normal native coronary arteries of similar size. Rings of small arteries and collateral vessels were suspended in baths, and tension was recorded. All rings were constricted with prostaglandin F2 alpha (3 microM) and subsequently exposed to cumulative concentrations of acetylcholine or bradykinin. In separate experiments, the procedure was repeated in the presence of 300 microM NG-monomethyl-L-arginine (L-NMMA) to inhibit endothelium-mediated vasodilation. Endothelium-dependent relaxation was further studied in the presence of indomethacin, and endothelium-independent relaxation was examined with sodium nitroprusside. Acetylcholine and bradykinin relaxed both normal native and collateral rings. In preconstricted small arteries and collateral vessels the concentration at 50% of maximal response of acetylcholine was 85.5 +/- 19.5 and 61.0 +/- 14.0 microns, and bradykinin was 11.9 +/- 7.4 and 10.7 +/- 2.1 microns, respectively. L-NMMA attenuated the response to acetylcholine and bradykinin in both groups. The results indicate that endothelium is present and functional in canine coronary collateral vessels. Both small coronary arteries and collateral vessels are equally responsive to endothelium-dependent vasodilators and inhibition of endothelium-dependent relaxing factor.

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