Candesartan restores pressure-induced vasodilation and prevents skin pressure ulcer formation in diabetic mice.

Background: Angiotensin II type 1 receptor (AT1R) blockers have beneficial effects on neurovascular complications in diabetes and in organ's protection against ischemic episodes. The present study examines whether the AT1R blocker candesartan (1) has a beneficial effect on diabetes-induced alteration of pressure-induced vasodilation (PIV, a cutaneous physiological neurovascular mechanism which could delay the occurrence of tissue ischemia), and (2) could be protective against skin pressure ulcer formation.

Methods: Male Swiss mice aged 5-6 weeks were randomly assigned to four experimental groups.

Erythropoietin restores C-fiber function and prevents pressure ulcer formation in diabetic mice.

Pressure-induced vasodilatation (PIV), a cutaneous physiological neurovascular (C-fiber/endothelium) mechanism, is altered in diabetes and could possibly contribute to pressure ulcer development. We wanted to determine whether recombinant human erythropoietin (rhEPO), which has protective neurovascular effects, could prevent PIV alteration and pressure ulcer formation. We developed a skin pressure ulcer model in mice by applying two magnetic plates to the dorsal skin.

Protective effect of candesartan in experimental ischemic stroke in the rat mediated by AT2 and AT4 receptors.

Objectives: The contribution of the AT2 and AT4 angiotensin receptors to the protective role of the AT1 receptor blocker candesartan in acute ischemic stroke was investigated.

Methods: Embolic stroke was induced by injection of calibrated microspheres (50 microm) in the right internal carotid in Sprague-Dawley rats.

Results: Inhibition of production of endogenous angiotensins by pretreatment for 24 h with lisinopril significantly increased mortality and infarct volume, whereas candesartan for 24 h reduced blood pressure to the same extent but had no deleterious effect.

Synergistic protective effects of erythropoietin and olmesartan on ischemic stroke survival and post-stroke memory dysfunctions in the gerbil.

Objectives: Treatment with erythropoietin and AT1 blockers is protective in experimental acute cerebral ischemia, with promising results in pilot clinical studies in human stroke. This paper examines the effects of using both agents as combination therapy in acute ischemic stroke.

Methods: We used the single carotid ligation stroke model in the gerbil.

Cerebroprotective effect of angiotensin IV in experimental ischemic stroke in the rat mediated by AT(4) receptors.

Recent studies have reported potential roles of angiotensins in an adaptative physiological mechanism of protection against cerebral ischemia-induced neurological damages. In the present study, we examined the protective role of angiotensin IV (AngIV) in a rat model of embolic stroke induced by intracarotid injection of calibrated microspheres (50 microm). Internal carotid infusions of increasing doses of AngIV (0.

Vasoconstrictive effect of angiotensin IV in isolated rat basilar artery independent of AT1 and AT2 receptors.

The effect of angiotensin IV (AngIV) was studied in freshly isolated rat basilar arteries (BAs) perfused at a constant rate. AngIV had no effect on basal BA perfusion pressure, but induced a marked concentration-dependent contraction in vessels precontracted by a 50-mM KCl solution (EC50=44.5+/-16 nM).

[The renin-angiotensin system: current data].

The renin-angiotensin system (RAS) is a major physiological regulator of vascular tone and is implicated in cardiovascular pathophysiology. More recently, basic research has however continuously extended our understanding of the complexicity of the systemic and tissular RASs. The peptid hormone, angiotensin II, acts primarily via type I (AT1) and type II (AT2) angiotensin receptors.

Acetylcholine-induced relaxation of rabbit basilar artery in vitro is rapidly reduced by reactive oxygen species in acute hyperglycemia: role of NADPH oxidase.

We examined the effects of acute hyperglycemia on the function of rabbit cerebral arteries in vitro. It was hypothesized that increased formation of reactive oxygen species (ROS) could occur, which could explain how hyperglycemia aggravates certain pathologic situations such as cerebral ischemia. Three-millimeter basilar artery segments were incubated in either normoglycemic (NG, 5.

Critical role of endothelial nitric oxide synthase and cyclooxygenase in response of rabbit basilar artery to serotonin.

The modes of action of serotonin (5-HT) on the tone of the rabbit basilar artery were investigated in vitro with the aim of determining the exact role of the endothelium. After sacrificing the animal under pentobarbital anesthesia, 3-mm segments of the artery were removed and mounted in a 5-ml myograph for isometric tension recording. Vessels precontracted by histamine were relaxed by acetylcholine.

NO-steroids: potent anti-inflammatory drugs with bronchodilating activity in vitro.

The synthesis of nitric oxide (NO) releasing anti-inflammatory molecules is an innovative strategy to design novel anti-inflammatory drugs. These compounds slowly release NO, via an enzymatic pathway conferring new biological activities. Here we report the potent anti-inflammatory profile and the bronchodilator effect of nitro-derivatives of steroids, prednisolone, especially.

[17B-estradiol and hypercholesterolemia: involvement of nitric oxide].

The mechanisms of the protective effect of 17B-estradiol were investigated in the middle cerebral artery (MCA) and aorta isolated from cholesterol-fed rabbits. Three groups were assigned: control group (standard chow), cholesterol group (standard chow+1% cholesterol) and estradiol group (1% cholesterol+17B-estradiol). The MCA and the aorta were isolated, precontracted respectively with high K(+) solution or with phenylephrine and exposed to cumulative acetylcholine concentrations.

Involvement of potassium channels in the protective effect of 17beta-estradiol on hypercholesterolemic rabbit carotid artery.

The involvement of endothelium-derived hyperpolarizing factor (EDHF) in the protective effect of 17beta-estradiol was investigated on the phenylephrine-precontracted carotid artery from cholesterol fed rabbits. Animals were fed for 8 weeks as follows: control group, standard chow; (control+estradiol) group, standard chow+17beta-estradiol; standard chow+1% cholesterol, cholesterol group; or (cholesterol+estradiol) group, 1% cholesterol chow+17beta-estradiol. Relaxations to acetylcholine (ACh) (3 nM-30 microM) were performed with N(omega) nitro-L-arginine methyl ester (300 microM) and indomethacin (10 microM).

Involvement of cyclooxygenase 2 in the protective effect of 17beta-estradiol on hypercholesterolemic rabbit aorta.

The involvement of cyclooxygenase (COX) in the effects of 17beta-estradiol was investigated on hypercholesterolemic rabbits aorta. Acetylsalycilic acid, nimesulide, or SQ22536 was used as respective antagonist of COX-1, COX-2, or adenylate cyclase using aortic rings precontracted with phenylephrine and exposed to cumulative concentrations of acetylcholine (ACh). The relaxation effect of ACh was impaired by hypercholesterolemia and restored by an 8-week 17beta-estradiol treatment.

Effects of treatment with 17beta-estradiol on the hypercholesterolemic rabbit middle cerebral artery.

Objective: The effects of acute and long-term treatment with 17beta-estradiol on the vasomotor responses of rabbit middle cerebral artery (RMCA) were investigated.

Methods: For 8 weeks, male rabbits consumed standard chow (control group), standard chow+1% cholesterol (cholesterol group) or 1% cholesterol chow+17beta-estradiol (i.m.

The protective effect of 17 beta-estradiol on vasomotor responses of aorta from cholesterol-fed rabbit is reduced by inhibitors of superoxide dismutase and catalase.

The involvement of endogenous antioxidant enzymes in the protective effect of 17 beta-estradiol against hypercholesterolemia was evaluated on aorta from cholesterol-fed rabbits treated with estradiol. 17 beta-Estradiol, more potent than alpha-tocopherol, restored the acetylcholine-induced relaxation, which was impaired by cholesterol chow, and enhanced the vasorelaxation induced by sodium nitroprusside. Diethyldithiocarbamate (5 mM), a superoxide dismutase (SOD) inhibitor, reduced relaxation to acetylcholine down to the level obtained in cholesterol-fed rabbits not treated with estrogen.

Reduction of the pressor response to nicotine in the guinea pigs by a histamine (H3) agonist is attenuated by an inhibitor of nitric oxide synthesis.

We examined whether a histamine (H3)-agonist, (R) alpha-methylhistamine, [(R) alpha-MeHA] reduced the pressor responses induced by nicotine in urethane-anesthetized guinea pigs treated by atropine. Nicotine dose-dependently increased the basal mean arterial pressure (MAP) and the heart rate (HR) of the preparation. Both effects were due to stimulation of sympathetic ganglia, since muscarinic receptors were blocked.

[Pharmacological approach of histamine H3 receptors: use of arterial and bronchiolar perfusion technique].

The actions of histamine were believed to be mediated by H1 and H2 receptors, until the discovery of a novel class named H3 in the central nervous system. Initially identified as presynaptic autoreceptors, now, evidence has been obtained drawing that H3 receptors are also located on non histaminergic neurons in the brain and in peripheral organs. In the present study, H3 responses are studied on arterial and bronchiolar segments perfused at constant rate.

NG-nitro-L-arginine methyl ester inhibits the effect of an H3-histaminergic receptor agonist on NANC contraction in guinea-pig perfused bronchioles.

A role for nitric oxide in the H3-histaminergic agonist-induced inhibition of the non-adrenergic, non-cholinergic (NANC) contraction has been studied in guinea-pig perfused bronchioles. (R)-alpha-Methylhistamine ((R)-alpha-MeHA), an agonist for H3 receptors, inhibited the NANC contraction induced by electrical field stimulation. NG-Nitro-L-arginine methyl ester (L-NAME) (50 microM), an inhibitor of nitric oxide synthesis, blocked the effect of (R)-alpha-MeHA.

Effect of an histaminergic H3 agonist on the non-adrenergic non-cholinergic contraction in guinea-pig perfused bronchioles.

From the bronchioles of guinea-pigs, preparations were isolated for registration of perfused pressure on electrical field stimulation (EFS) and by application of drugs. The perfused bronchioles contracted when EFS was applied in the presence of atropine and phentolamine suggesting a non-adrenergic non-cholinergic (NANC) response. (R)-alpha-Methylhistamine (methylhistamine), a selective H3 agonist, reduced the NANC bronchoconstrictor response in a concentration-dependent manner.

Histamine H3 agonist decreases arterial blood pressure in the guinea-pig.

Intravenous injection of an H3-agonist, (R)-alpha-methylhistamine, dose-dependently caused a transient fall in mean arterial pressure of guinea-pigs. This pressor response was not reduced by combined mepyramine/cimetidine (up to 1 mg kg-1), atropine or propranolol, but was attenuated by either a selective H3-antagonist, thioperamide, or a competitive inhibitor of nitric oxide synthesis, NG-monomethyl L-arginine. The reduction by the inhibitor of nitric oxide synthesis was reversed by L- but not D-arginine.