Biomedical subjects

J F Bouchard

Publications and source records attributed to J F Bouchard.

6 recordsLinked to original sources

PubMed1998

Protection afforded by preconditioning to the diabetic heart against ischaemic injury.

OBJECTIVE: The aim of this study was to assess whether the cardioprotective effect of ischaemic preconditioning (IPC) on endothelial function in coronary arteries and myocardial function is affected in the streptozotocin-induced diabetic rat heart. METHODS: Isolated hearts, perfused under constant flow conditions, were exposed to 30 min of partial ischaemia (flow rate 1 ml min-1) followed by 20 min of reperfusion. RESULTS: In the diabetic group (without ischaemia or IPC), infusion of 10 microM serotonin (5-HT), an endothelium-dependent, and 3 microM sodium nitroprusside (SNP), an endothelium-independent vasodilator, in the coronary bed preconstricted with 0.1 microM U-46619 induced a marked vasodilation. Ischaemia, either without or with preconditioning with a single 5 min ischaemia and 10 min reperfusion (IPC1) before ischaemia, was accompanied by a reduced 5-HT-induced vasodilation in diabetic hearts. In contrast, IPC1 preserved the response to 5-HT in non-diabetic hearts. A more extensive IPC with 3 periods of 5 min ischaemia followed by 5 min reperfusion (IPC3) preserved the vasodilation produced by 5-HT in both diabetic and non-diabetic hearts. IPC3 increased the recovery of d P/dtmax and d P/dtmin during the 30 min ischaemic period and during reperfusion in all hearts. In contrast, IPC1 had no effect on myocardial recovery in either groups. Adenosine pre-treatment started 30 min before ischaemia mimicked IPC3, preserving the vasodilation to 5-HT and improving myocardium recovery in both groups. When adenosine was started 15 min before ischaemia, vasodilation to 5-HT was preserved in non-diabetic hearts only. CONCLUSIONS: These results suggest that IPC affords protection to endothelial function in resistance coronary arteries of diabetic hearts. To achieve this protection, a more extensive IPC is needed, which may be related to a longer exposure to adenosine.

Adenosine↗

PubMed1998

Role of kinins in the endothelial protective effect of ischaemic preconditioning.

1. The aim of this study was to assess whether the protective effect of ischaemic preconditioning on endothelial function in coronary arteries of the rat involves kinins. 2. Isolated hearts of the rat were exposed to a 30-min low-flow ischaemia (flow rate of 1 ml min[-1]) followed by 20-min reperfusion, after which coronaries were precontracted with 0.1 microM U-46619, and the response to the endothelium-dependent vasodilator, 5-hydroxytryptamine (5-HT, 10 microM), compared to that of the endothelium-independent vasodilator, sodium nitroprusside (SNP, 3 microM). 3. In untreated hearts, ischaemia-reperfusion diminished selectively 5-HT-induced vasodilatation, compared with time-matched sham hearts. The vasodilatation to SNP was unaffected after ischaemia-reperfusion. Preconditioning (5 min of zero-flow ischaemia followed by 10 min reperfusion) in untreated hearts preserved the vasodilatation produced by 5-HT. 4. Blockade of B1 and B2 receptors with either 3 nM [Lys[0], Leu8, des-Arg9]-bradykinin (LLDBK) or 10 nM Hoe 140 (icatibant), respectively, (started 15 min before ischaemic preconditioning or a corresponding sham period and stopped just before the 20-min reperfusion period) had no effect on the vasodilatation produced by either 5-HT or SNP in sham hearts. Pretreatment with Hoe 140 did not block the protective effect of ischaemic preconditioning on the 5-HT vasodilatation. In contrast, LLDBK halved the protective effect of ischaemic preconditioning on endothelium-dependent vasodilatation. 5. Perfusion with either bradykinin or des-Arg9-bradykinin (1 nM) 30 min before and lasting throughout the ischaemia protected the endothelium. 6. In conclusion, ischaemic preconditioning affords protection to the endothelial function in coronary resistance arteries of the rat partly by activation of B1 receptors. Although exogenous BK perfusion can protect the endothelium, B2 receptors do not play an important role in this protection in the rat isolated heart.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1998

[Role of B1 receptors in the endothelial protective effect of ischaemic preconditioning].

The aim of this study was to assess whether the cardioprotective effect of ischaemic preconditioning (IPC) on endothelial function in resistance coronary arteries of the rat involves activation of kinin receptors. Isolated rat hearts perfused under constant flow conditions were exposed to 30 min of partial ischaemia (flow rate 1 mL/min) followed by 20 min of reperfusion. Preconditioning was performed with 5 min zero-flow ischaemia and 10 min reperfusion before the 30-min ischaemia. After the 20-min reperfusion period, coronaries were precontracted with U-46619 0.1 microM, and the coronary response to the endothelium-dependent vasodilator, serotonin (5-HT, 10 microM), was compared to that of the endothelium-independent vasodilator, sodium nitroprusside (SNP, 3 microM). Kinin B1 and B2 receptors were blocked with perfusion of either [Lys0, Leu8, des-Arg0]-Bradykinin 30nM (LLDBK) or Hoe 140 10 nM (Hoe) respectively, started 15 min before IPC or a corresponding sham period and stopped just before the 20-min reperfusion period. In untreated hearts, ischemia diminished selectively 5-HT-induced vasodilatation, compared to sham hearts (without ischaemia). The vasodilatation by SNP was unaffected after ischaemia and reperfusion. Preconditioning in untreated hearts preserved the vasodilatation produced by 5-HT. Treatment of hearts with either Hoe or LLDBK had no effect on the vasodilatation produced by both 5-HT and SNP in sham hearts. Pre-treatment with Hoe did not block the protective effect of IPC on the 5-HT vasodilatation. LLDBK halved the protective effect of IPC on endothelium-dependent vasodilatation. In addition, the protective effect of BK on the endothelial function in the isolated rat heart was blocked by LLDBK. These results suggest that IPC and exogenous kinin perfusions afford protection to endothelial function in resistance coronary arteries of the rat partially by activation of B1 kinin receptors. B2 receptors do not play any role in that protection.

Animals↗

PubMed1997

[Decrease of vascular response to iloprost in diabetic rats].

The functional dilatory response in the streptozotocin-induced diabetic rat was investigated using thoracic aortas and coronary microcirculation. The aortas were cut in 4 mm intact or denuded rings and mounted into 20-ml organ baths. Coronary microcirculation was evaluated with isolated hearts perfused under constant flow conditions. Firstly, vasodilation to iloprost (Ilo) was examined. Dose-response curves to Ilo (10 pM-10 microM) on phenylephrine (PE, 30 nM for endothelium-denuded, and 0.3 microM for intact) preconstricted rings of diabetics and age-matched controls were comparable (n = 6). Decreased vasodilation in diabetic group was observed when dose-response curves to Ilo (1 nM-0.1 microM) were realized in isolated hearts (-22 +/- 3.3% vs -46 +/- 3.9%, n = 6, p < 0.05). Secondly, dose-response curves to forskolin (FSK), an adenylate-cyclase activator, performed in hearts (1 nM-3 microM), and on PE preconstricted rings (10 pM-10 microM) of diabetics and age-matched controls were comparable. Finally, the effect of an activator of ATP sensitive potassium channels (KATP), cromakalim (CMK), was evaluated in coronary circulation (0.3 nM-3 microM) and in aortas (10 pM-10 microM). Decreased vasodilation to CMK was observed in diabetic hearts (-10.5 +/- 4.3 vs -30.1 +/- 2.8%, n = 6, p < 0.05). In conclusion, under our experimental conditions, diabetes affects selectively the coronary vasodilation to iloprost. This modification of vascular reactivity may be due to a decrease of KATP channels sensitivity but not to a decreased activity of adenylate-cyclase.

Adenosine Triphosphate↗

PubMed1996

Mechanisms of protection afforded by preconditioning to endothelial function against ischemic injury.

The aim of this study was to assess whether the cardioprotective effect of ischemic preconditioning (IPC) on endothelial function in resistance coronary arteries of the rat involves adenosine and/or activation of ATP-sensitive K+ channels (KATP channels). Isolated rat hearts perfused under constant-flow conditions were exposed to 30 min of partial ischemia (flow rate 1 ml/min) followed by 20 min of reperfusion. Preconditioning was performed with 5 min of ischemia and 10 min of reperfusion before the 30-min ischemia. After the 20-min reperfusion period, coronary arteries were precontracted with U-46619 (0.1 microM), and the coronary response to the endothelium-dependent vasodilator serotonin (5-HT; 10 microM) was compared with that of the endothelium-independent vasodilator sodium nitroprusside (SNP; 3 microM). KATP channels or adenosine receptors were blocked with perfusion of either glibenclamide (0.3 microM) or 8-phenyltheophylline (8-PT; 5 microM), respectively, starting 15 min before IPC or a corresponding sham period. In untreated hearts, ischemia selectively diminished 5-HT-induced vasodilation, compared with sham hearts (without ischemia). The vasodilation by SNP was unaffected after ischemia and reperfusion. Preconditioning in untreated hearts preserved the vasodilation produced by 5-HT. Treatment of hearts with either glibenclamide or 8-PT halved the vasodilation produced by both 5-HT and SNP in sham hearts. Glibenclamide reduced by one-half, whereas 8-PT completely blocked, the protective effect of IPC on endothelium-dependent vasodilation. These results suggest that IPC affords protection to endothelial function in resistance coronary arteries of the rat partially by activation of KATP channels. Adenosine plays a major role in that protection.

Adenosine Triphosphate↗

PubMed1994

Evidence that prostaglandins I2, E2, and D2 may activate ATP sensitive potassium channels in the isolated rat heart.

OBJECTIVE: The aim was to study the contribution of ATP sensitive potassium channels (KATP channels) in the coronary vasodilatation produced by prostaglandins I2, E2, and D2 in rats. METHODS: Isolated Langendorff rat hearts, perfused under constant flow conditions, and rat aortic rings were used. Dose-response curves to PGE2, PGD2, and iloprost, a PGI2 analogue, were performed before and during KATP channel blockade with glibenclamide. Arachidonic acid was used to increase the formation of endogenous PGI2. RESULTS: Infusions of PGE2, PGD2, and iloprost in isolated hearts induced marked vasodilatation, as reflected by the reduction in coronary perfusion pressure of 27(SEM 7), 30(6), and 43(6)%, for 0.1 microM PGE2, PGD2, and iloprost, respectively. Infusion of glibenclamide (0.3 microM) was accompanied by a 23(3)% increase in coronary perfusion pressure. The vasodilatation induced by levcromakalim (0.1 microM) was completely inhibited in the presence of glibenclamide, whereas that of papaverine (30 microM) was unaffected. Glibenclamide significantly reduced the vasodilatation induced by iloprost (at 3 to 100 nM), PGE2 (30 and 100 nM), and PGD2 (30 and 100 nM), at all concentrations studied. In contrast, glibenclamide (1 microM) had no effect on iloprost induced relaxation of aortic rings. Arachidonic acid infusion (from 0.1 to 3 microM) in isolated hearts induced a pronounced vasodilatation and a significant release of 6-keto-PGF1 alpha into the coronary effluent in a dose dependent fashion. Both responses to arachidonic acid were significantly reduced in the presence of the cyclo-oxygenase inhibitor diclofenac (1 microM). In an additional experimental series, the vasodilatation induced by arachidonic acid infusions was found to be significantly reduced in the presence of glibenclamide. CONCLUSIONS: Glibenclamide is a potent inhibitor of the coronary dilator action of prostaglandins I2, E2, and D2. This observation suggests that these prostaglandins may cause vasodilatation by opening KATP channels.

Adenosine Triphosphate↗