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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The functions of the endothelium and the effects of hypertension, atherosclerosis, and diabetes on the endothelium are reviewed. The endothelium affects vascular tone by releasing vasodilators and modulating the effects of vasoactive substances such as catecholamines, bradykinin, serotonin, and angiotensin II. Relaxation of vascular smooth muscle depends upon a functionally intact endothelium and the release of the endothelium-derived relaxing factor nitric oxide. Endothelial cells also appear to release a hyperpolarizing factor that relaxes smooth muscle through activation of the sodium-potassium pump, and of the endothelium-dependent contracting factors. Similarities are found in the vascular injury resulting from hypertension, atherosclerosis, and diabetes. When these risk factors coexist, they can act synergistically and magnify the vascular injury. The endothelium appears to be one of the major targets for these forms of injury. Future therapeutic strategies will focus on ways to prevent, arrest, or reverse endothelial injury.
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PMID:Hypertension, endothelium, and cardiovascular risk factors. 199 9

More than 10 years of clinical experience using angiotensin-converting-enzyme (ACE) inhibitors have shown that this class of drug does not have any adverse metabolic effects on carbohydrate and lipid metabolism. Rather, a number of studies on patients with essential hypertension or non-insulin-dependent diabetes mellitus have indicated minor improvements in glucose homeostasis and correction of dyslipidaemia. Some recent studies using the euglycaemic insulin clamp technique have indicated that the beneficial effect of captopril, the most extensively studied drug, is exerted on insulin sensitivity, a site with the potential to influence glucose and lipid metabolism. There is no uniform explanation for this action of captopril, but increased blood flow in skeletal muscle, accumulation of bradykinin or more efficient insulin release may be suggested as potential modes of action. It remains to be established whether this effect of captopril can be extrapolated to other ACE inhibitors, and the extent to which effects on insulin sensitivity will influence the long-term consequences for future risk of diabetes mellitus and coronary heart disease in patients with essential hypertension.
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PMID:Metabolic effects of ACE inhibitors. 204 20

The great discovery by Furchgott of the relaxing factor released from the endothelium (EDRF) awakened us to the necessity to reevaluate the functional importance of endothelial cells that have been chemically or physically stimulated. EDRF was first demonstrated to be released by acetylcholine, substance P, bradykinin and calcium ionophore A23187; thereafter, many substances have been found to release EDRF. This factor is quite unstable, is not produced by cyclooxygenase, and is an activator of soluble guanylate cyclase that synthesizes cyclic GMP; its action is suppressed by antioxidants via the superoxide anions produced, potentiated by superoxide dismutase and abolished by methylene blue and oxyhemoglobin. Recently, the role of lipoxygenase products in the production of EDRF was evaluated with new 5-lipoxygenase inhibitors without antioxidant activity. During the last couple of years, the actions and chemical properties of EDRF were verified to be quite similar to those of nitric oxide (NO); therefore, the hypothesis of "EDRF = NO" is widely being accepted. NO is produced from L-arginine via catalysis by an enzyme that is activated by Ca2+. The enzyme activity is inhibited by L-monomethyl arginine and other L-arginine analogs. Chemical and physical stimulations increase intracellular Ca2+ in endothelial cells that seems to be associated with K(+)-channel opening and hyperpolarization. Current interests are directed to the possible roles of NO in the regulation of nerve function. There are evidences suggesting that NO modulates adrenergic nerve function in blood vessels and some brain cell functions regulated by cellular cyclic GMP. Particularly, NO may be a transmitter substance in non-adrenergic, non-cholinergic vasodilator nerves innervating the cerebral arteries. Future investigations will determine the physiological roles of EDRF or NO and its relationships to pathophysiology of vascular dysfunctions, such as vasospasm and those related to hypertension, diabetes, aging, etc., and the extended roles of NO in nerve function, inflammation, immune reactions, etc. would be clarified more extensively by accelerated progress in this field of research.
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PMID:[Endothelium-derived relaxing factor (EDRF)]. 216 93

Amylin amide, a 37-amino acid peptide that is a major component of amyloid deposits in the diabetic pancreas, possesses vasodilator activity. Human synthetic amylin amide (30 to 300 pmol/site) stimulated a dose-dependent increase in blood flow after intradermal injection in rabbit skin. Amylin amide was 100 times less active than the structurally related potent vasodilator neuropeptide calcitonin gene-related peptide. Amylin amide did not induce edema formation; however, as a consequence of its vasodilator activity, amylin amide potentiated edema formation induced in rabbit skin by bradykinin. The intravenous injection of amylin amide (10 nmol) caused a systemic drop in blood pressure. This study demonstrates that amylin amide elicits vasodilator responses in vivo. It is possible that the release of amylin amide from the pancreas in type II diabetes could lead to changes in vascular tone.
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PMID:The demonstration of vasodilator activity of pancreatic amylin amide in the rabbit. 231 20

The role of renal vasoregulatory hormones in the hyperfiltration of early insulin-dependent diabetes mellitus (IDDM) was studied by micropuncture methods in rats with streptozotocin-induced diabetes. Seven to ten days after streptozotocin injection, untreated diabetic rats had elevated glomerular filtration rate (GFR) and single-nephron glomerular filtration rate (SNGFR), compared with normal euvolemic rats. Infusion of indomethacin (5 mg/kg) markedly reduced urinary and proximal tubular fluid prostaglandin E2 (PGE2), but GFR and SNGFR did not change. In a second group, intrarenal infusion of aprotinin (1,000 kallikrein inhibitor units.min-1.kg-1) to inhibit kallikrein also had no effect on GFR or SNGFR. In a third group, intrarenal infusion of angiotensin II (ANG II, 0.1 microgram.min-1.kg-1) reduced GFR, renal plasma flow (RPF), SNGFR, and glomerular plasma flow rate (QA) to values close to those in normal euvolemic rats. Single-nephron filtration fraction rose significantly with ANG II, but glomerular pressure (PG) was unaltered. Tubular fluid PGE2 increased in response to ANG II. Saralasin infusion following ANG II returned GFR, RPF, SNGFR, and QA to supernormal levels, and PG fell. In chronically salt-loaded normal rats, the responses to intrarenal ANG II and saralasin were similar to those observed in the diabetic rats. We conclude that hyperfiltration in early IDDM is not dependent on intact renal PGE2 or bradykinin synthesis. The results with ANG II infusion indicate that pre- and postglomerular and glomerular contractile cells of the diabetic kidney are able to constrict in response to this hormone.
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PMID:Vasoregulatory hormones and the hyperfiltration of diabetes. 244 21

The recent discovery of endothelium-derived relaxation factor (EDRF) has altered the traditional classification of vasodilators used in angina pectoris and heart failure. If a vasodilator induces release of EDRF from the epithelium it is classified as endothelium-dependent, if not it is independent. Sodium nitroprusside and SIN-1 (active metabolite of molsidomine) are the main independent vasodilators since the endothelium relaxation factor appears to be principally a nitric oxide radical in these synthetic vasodilators. In contrast, calcium-channel blockers and a good number of endogenous chemical mediators (acetylcholine, bradykinin, serotonin, etc.) are endothelium-dependent. Furthermore, simple increase in blood flow through the large vessels can result in endothelium-dependent vasodilation (flow rate-dependence) the extent of which depends on the drug examined. The fact that the pharmacologic response of a vasodilator can be altered under certain pathologic conditions (atherosclerosis, hypertension, diabetes, etc.) further increases the importance of the role of the vascular endothelium in the action of vasodilators since endothelial modulation may then be completely diverted to secretion of endothelium-derived contracting factors (EDCFS).
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PMID:[Vasodilator agents and the vascular endothelium]. 262 13

This report describes the case of a 70-year-old female suffering from diabetes mellitus and dilatative cardiomyopathy with congestive heart failure. It is likely that alveolar-capillary membrane damage occurred apart from cardiac involvement. Diffuse interstitial pulmonary fibrosis subsequently occurred with consequent acute progressive respiratory failure and death. The cause of the damage to the alveolar-capillary membranes is still unknown and we thought that long-term administration of captopril might have contributed to the damage itself, since like all ACE-inhibitors, captopril is able to bring about tissular storage of both bradykinin and prostaglandins and therefore alter the pulmonary reactivity to phlogistic stimuli.
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PMID:[Acute progressive respiratory insufficiency caused by diffuse interstitial pulmonary disease in a diabetic patient with dilated myocardiopathy]. 270 34

Complications of the gastrointestinal tract in patients with diabetes mellitus can cause marked discomfort and may modify the ability of the patient to maintain normal glucostasis. In an attempt to elucidate some of the factors causing gastrointestinal dysfunction in experimental diabetes we examined the responses of jejunal smooth muscle in streptozotocin-induced diabetes in rats to some of the neurotransmitters and autocoids found in the enteric nervous system. Jejunal tissues from 4- to 5-week diabetic rats were examined for their responses to neurokinin (NK) A, NKB, substance P (SP), bradykinin, neurotensin, bethanechol, isoproterenol and phenylephrine. The affinities for all these agonists, except for SP which increased slightly with diabetes, were the same in both control and diabetic tissues. NKA was the most potent neurokinin and elicited the largest contractile responses from jejunal tissues of both control and diabetic animals. The contractile response to NKA, but not that to NKB or SP, was increased in the jejunum from diabetic animals. Part of this increased responsiveness was antagonized by atropine. The contractile effects of the cholinergic agonist, bethanechol, were not altered by the diabetic state. Decreased relaxation responses in the jejunum from diabetic animals were observed for bradykinin, neurotensin and isoproterenol, but not for phenylephrine. These results suggest that the myogenic actions of several agonists are modified in experimental diabetes.
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PMID:Modified smooth muscle responses of jejunum in streptozotocin-diabetic rats. 290 44

Angiotensin-converting enzyme, the polypeptide that converts angiotensin I to angiotensin II, was measured in the serum of 114 pregnant women who had normal blood pressure, pregnancy-induced hypertension-preeclampsia, and chronic hypertension with or without pregnancy-induced hypertension. Angiotensin-converting enzyme levels were unrelated to weeks of gestation. The angiotensin-converting enzyme levels were similar in normotensive women (21.1 +/- 6.9 units/ml), women with chronic hypertension without pregnancy-induced hypertension (23.1 +/- 2.7 units/ml), and patients with pregnancy-induced hypertension where magnesium sulfate (22.6 +/- 8.7 units/ml) had been administered prior to angiotensin-converting enzyme assay, but these values were significantly less than those in patients with pregnancy-induced hypertension with no magnesium sulfate (29.1 +/- 6.5 units/ml) therapy and in women with chronic hypertension with superimposed pregnancy-induced hypertension (30.7 +/- 4.4 units/ml) (p less than 0.005). Maternal venous and umbilical venous and arterial angiotensin-converting enzyme levels were as follows: The maternal venous level was less than the cord venous level and greater than the cord arterial value. Neither neonatal size nor twin gestation influenced the angiotensin-converting enzyme levels. Patients with diabetes mellitus had variable angiotensin-converting enzyme values regardless of the status of the blood pressure. The physiologic theories of blood pressure control in pregnant women are discussed in relation to the renin-angiotensin, bradykinin, and prostaglandin systems.
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PMID:The relation of angiotensin-converting enzyme to the pregnancy-induced hypertension-preeclampsia syndrome. 300 58

Effect of metoclopramide (MCP), a dopaminergic antagonist, on orthostatic hypotension associated with diabetes mellitus, was investigated to prove its plausible role of renin-angiotensin-aldosterone and catecholamine activation by comparative study in 6 diabetics with orthostatic hypotension (OH) and 9 diabetics without OH. With MCP treatment, drop of systolic blood pressure (SBP) on standing was significantly improved. However, the postural responses of plasma renin activity (PRA), plasma aldosterone and norepinephrine were not enhanced by MCP treatment. Moreover, MCP treatment did not modify the vascular reactivity to the exogenously infused angiotensin II and norepinephrine. Thus, it would be interesting to speculate that MCP can improve SBP through its suppressive effect on some depressor substance(s) such as bradykinin which liberates exaggeratively in diabetic OH.
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PMID:Effect of metoclopramide on orthostatic hypotension in diabetes mellitus: failure to demonstrate the role of vasoconstrictive hormones. 304 7


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