Effects of salsalate therapy on recovery from vascular injury in female Zucker fatty rats.

Objective: Salsalate is a dimeric form of salicylic acid that has been shown to have anti-inflammatory activity and to reduce glucose levels, insulin resistance, and cytokine expression. However, the effect of salsalate on vascular injury has not been determined. The objective of this study is to investigate the effect of salsalate on vascular injury and repair in a rat model of carotid artery balloon catheter injury.

The synthetic GLP-I receptor agonist, exenatide, reduces intimal hyperplasia in insulin resistant rats.

We studied the effect of a synthetic GLP-1 receptor agonist, exenatide, a drug approved for the treatment of type 2 diabetes, on the recovery from vascular injury in Zucker (non-diabetic) fatty rats. Exenatide 5.0 microg/kg per day or saline was administered for seven days before, and 21 days after balloon catheter mediated carotid injury.

U74389F, a 21-aminosteroid antioxidant, improves neoendothelial morphology, but not neointimal thickening after balloon catheter injury.

U74389F is a compound in a family of 21-aminosteroids devoid of classical glucocorticoid action that inhibit lipid peroxidation. These compounds improve neurologic function and tissue survival after head or spinal cord injury. Dexamethasone inhibits development of intimal hyperplasia (IH) and improves attenuated nitric oxide (NO) production of the rabbit aorta subsequent to balloon catheter injury.

Insulin glargine reduces carotid intimal hyperplasia after balloon catheter injury in Zucker fatty rats possibly by reduction in oxidative stress.

Diabetes and impaired glucose tolerance are associated with increased cardiovascular disease morbidity and mortality particularly after vascular injury. Since insulin is frequently used in such patients, the effect of glulisine (short acting) and glargine (long acting) were tested in Zucker fatty rat carotid artery subjected to balloon catheter injury. Insulin-resistant Zucker fatty rats were sc injected 0.

Animal models of catheter-induced intimal hyperplasia in type 1 and type 2 diabetes and the effects of pharmacologic intervention.

Diabetes is a complex disorder characterized by impaired insulin formation, release or action (insulin resistance), elevated blood glucose, and multiple long-term complications. It is a common endocrine disorder of humans and is associated with abnormalities of carbohydrate and lipid metabolism. There are two forms of diabetes, classified as type 1 and type 2.

Effect of pharmacological treatments for diabetes on homocysteine.

Hyperhomocysteinemia is a well-established risk factor for cardiovascular disease. The association of hyperhomocysteinemia with diabetes mellitus is complex and may explain some of the risk of CVD in diabetics not explained by traditional risk factors. Both modifiable and non-modifiable factors interact with homocysteine metabolism and determine the plasma homocysteine concentrations.

Methods in assessing homocysteine metabolism.

Homocysteine, a sulfur-containing amino acid, is a metabolite of the essential amino acid methionine. High blood levels of homocysteine result in far-reaching biochemical and life-threatening consequences. Homocysteine exists at a critical biochemical intersection in the methionine cycle between S-adenosylmethionine, the ubiquitous methyl donor, and vitamins B(12) and folic acid.

Hyperhomocysteinemia exacerbates the development of intimal hyperplasia in Sprague-Dawley rats: Alleviation by rosiglitazone.

The amino acid intermediate homocysteine (Hcy) is formed during the metabolism of methionine to cysteine. Hyperhomocysteinemia (HHcy) is recognized as an independent risk factor for coronary atherosclerosis. The circulating levels of total Hcy (tHcy) can increase due to intake of foods rich in methionine or deficiencies of vitamins such as folate, pyridoxine and cyanocobalamin, which are required for the metabolism of Hcy.

Rosiglitazone reduces serum homocysteine levels, smooth muscle proliferation, and intimal hyperplasia in Sprague-Dawley rats fed a high methionine diet.

Homocysteine (Hcy) is a metabolite of the essential amino acid methionine. Hyperhomocysteinemia is associated with vascular disease, particularly carotid stenosis. Rosiglitazone, a ligand of the peroxisome proliferator-activated receptor gamma , attenuates balloon catheter-induced carotid intimal hyperplasia in type 2 diabetic rats.

Effect of combination endothelial nitric oxide synthase gene therapy and sildenafil on erectile function in diabetic rats.

Erectile dysfunction associated with diabetes mellitus is caused in part by disordered endothelial smooth muscle relaxation, neuropathy, and a decrease in cavernosal nitric oxide synthase (NOS) activity. The purpose of this study was to determine whether a combination of sildenafil and adenoviral gene transfer of endothelial NOS (eNOS) could enhance the erectile response in diabetic rats. Five groups of animals were utilized: (1) age-matched control rats, (2) streptozotocin (STZ)-induced diabetic rats (60 mg/kg i.

Differential effects of peroxisome proliferator activator receptor-alpha and gamma ligands on intimal hyperplasia after balloon catheter-induced vascular injury in Zucker rats.

Background: Patients with type 2 diabetes mellitus have a higher rate of restenosis following angioplasty. Peroxisome proliferator activator receptor-alpha (PPAR) and gamma ligands such as fenofibrate and rosiglitazone, respectively, have been shown to have protective effects on the vessel wall. We studied the effect of fenofibrate and rosiglitazone on intimal hyperplasia in the Zucker rat, a model for insulin resistance and type 2 diabetes mellitus, following balloon catheter-induced injury.

A selective somatostatin type-2 receptor agonist inhibits neointimal thickening and enhances endothelial cell growth and morphology following aortic balloon injury in the rabbit.

Somatostatin analogs have been shown to inhibit vascular smooth muscle cell (VSMC) proliferation and attenuate neointimal thickening following experimental balloon catheter injury. In this study, the effects of a selective agonist for the somatostatin receptor subtype 2, PRL-2486, on neointimal thickening and endothelial cell regrowth 2 weeks following balloon catheterization of male New Zealand White rabbits were determined. Rabbits treated 2 days prior to and 2 weeks after catheter injury with 10 microg/kg/day PRL-2486 (PRL-tx) had decreased I/M ratios (intimal area/medial area x 100; p < 0.

Hormones and homocysteine.

Hyperhomocysteinemia is a well-established risk factor for cardiovascular disease. Various factors, both modifiable and non-modifiable, interact with the homocysteine metabolism and determine the plasma homocysteine concentrations. These include genetic abnormalities, age, sex and various nutritional and hormonal determinants, all of which play a role in atherosclerosis and accelerated peripheral and cardio-vascular disease (CVD).

The effect of troglitazone on plasma homocysteine, hepatic and red blood cell S-adenosyl methionine, and S-adenosyl homocysteine and enzymes in homocysteine metabolism in Zucker rats.

We studied the effect of troglitazone on the plasma concentrations of homocysteine (tHcy), the erythrocyte and hepatic concentrations of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), and the hepatic activities of cystathionine-beta-synthase (C beta S) and methylenetetrahydrofolate reductase (MTHFR) in lean and fatty Zucker rats (a model of insulin resistance). Four groups of female Zucker rats were studied. Troglitazone (200 mg/kg) was administered by gavage daily for 3 weeks to lean and fatty Zucker rats.

Drugs affecting homocysteine metabolism: impact on cardiovascular risk.

Elevated total plasma homocysteine has been established as an independent risk factor for thrombosis and cardiovascular disease. A strong relationship between plasma homocysteine levels and mortality has been reported in patients with angiographically confirmed coronary artery disease. Homocysteine is a thiol containing amino acid.

Analysis of responses to angiotensin II in the mouse.

Responses to angiotensin II (Ang II) were investigated in anaesthetised CD1 mice. Injections of Ang II caused dose-related increases in systemic arterial pressure that were antagonised by candesartan. Responses to Ang II were not altered by PD 123319.

Effects of low-dose candesartan on the rate of re-endothelialisation following vascular wound healing.

The wound healing response of the vascular wall to injury involves re-endothelialisation of the denuded luminal surface and thickening of the intimal area (intimal hyperplasia), as expressed by the intimal-to-medial area ratio (I/M). Candesartan, at doses of 1 mg/kg/day or higher, has been reported to attenuate the intimal hyperplastic response. We tested the hypothesis that candesartan, at doses lower than those associated with attenuation of intimal hyperplasia, may affect re-endothelialisation.

Cyclic GMP-dependent protein kinase expression in coronary arterial smooth muscle in response to balloon catheter injury.

Arterial smooth muscle cells undergo phenotypic and proliferative changes in response to balloon catheter injury. Nitric oxide (NO) and cGMP have been implicated in the inhibition of vascular smooth muscle cell proliferation and phenotypic modulation in cultured-cell studies. We have examined the expression of the major cGMP receptor protein in smooth muscle, cGMP-dependent protein kinase I (PKG), in response to balloon catheter injury in the swine coronary artery.

Balloon catheter vascular injury of the alloxan-induced diabetic rabbit: the role of insulin-like growth factor-1.

Neointimal thickening following catheter injury is characterized, in part, by growth factor-induced vascular smooth muscle cell (VSMC) proliferation. It was hypothesized that a reduction in serum insulin-like growth factor-1 (IGF-1), characteristic of chemically-induced diabetes, would result in decreased VSMC proliferation and attenuate neointimal thickening. It was found that alloxan-treated New Zealand White rabbits exhibit varying degrees of glycemia.

Analysis of Vasodepressor Responses to Nociceptin and Nociceptin Analogs in the Systemic Vascular Bed of the Anesthetized Rabbit In Vivo.

Background: The heptadecapeptide nociceptin, also known as Orphanin FQ, is a recently discovered endogenous ligand for the opioid-like G-protein-coupled receptor ORL(1). Methods and Results: In the present study, responses to nociceptin, [Tyr(1)]-nociceptin, nociceptin-(2-17), nociceptin-(1-11), and nociceptin-(1-7) were compared in the systemic vascular bed of the rabbit. Nociceptin and [Tyr(1)]-nociceptin induced dose related decreases in systemic arterial pressure (SAP) when injected in doses of 1-30 nmol/kg intravenous (IV); in terms of relative vasodepressor activity, [Tyr(1)]-nociceptin and nocicpetin were similar in potency.

Adrenomedullin Does Not Inhibit Human Platelet Aggregation.

BACKGROUND: Adrenomedullin (ADM) is a hypotensive peptide isolated from human pheochromocytoma extracts discovered in 1993 using an assay system designed to monitor its ability to increase rat platelet adenosine 3',5'-cyclic monophosphate (cAMP) levels. Physiological mediators that elevate cAMP levels, such as prostaglandin (PG)E(1) and PGI(2), have also been shown to inhibit platelet aggregation. Therefore, we have chosen to investigate the effect of ADM, a peptide shown to increase platelet cAMP levels, on human platelet aggregation.

Endothelial cell regrowth and morphology after balloon catheter injury of alloxan-induced diabetic rabbits.

Neointimal thickening after catheter injury has been reported to be influenced by the integrity of the vascular endothelium. We have previously shown that neointimal thickening is significantly reduced in alloxan-induced diabetic New Zealand White rabbits after catheter injury compared with euglycemic rabbits. In the present study, it was hypothesized that endothelial cell regrowth, morphology, and endothelium-dependent vasoreactivity after catheter injury are improved in the diabetic rabbit (glucose >/=400 mg/dl) compared with the euglycemic rabbit.

Analysis of the effects of candesartan on responses to angiotensin II in the hindquarters vascular bed of the cat.

The effects of the nonpeptide angiotensin II (AngII) AT1 receptor blocker candesartan on responses to AngII were investigated in the hindquarters vascular bed of the cat. Under constant-flow conditions, injections of AngII into the hindquarters perfusion circuit elicited dose-dependent increases in perfusion pressure. Candesartan in a dose of 3 microg/kg intravenously (i.