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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension appears to predispose to both atheroma and thrombus formation and is a risk factor for stroke and coronary artery disease. Insulin resistance and hyperinsulinaemia are also associated with hypertension, whether treated or untreated and irrespective of obesity. In an attempt to treat the possible insulin resistance in hypertension, an antidiabetic agent, metformin, which enhances glucose uptake, was given to non-obese, non-diabetic, untreated hypertensives in a pilot study. Metformin improved insulin sensitivity, decreased plasma insulin, serum cholesterol and triglycerides, increased fibrinolytic activity and markedly decreased blood pressure. These findings support the concept that insulin resistance may be important in cases of primary hypertension, i.e. those with concomitant metabolic and possibly also fibrinolytic abnormalities. Furthermore, the results indicate that insulin resistance may precede hypertension in these cases.
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PMID:Metformin and blood pressure. 158 82

Insulin resistance and hyperinsulinaemia may play an important role in both the development of hypertension and its accompanying metabolic aberrations. In order to investigate this possibility, nine non-obese, non-diabetic, non-smoking, middle-aged men with untreated hypertension were treated with metformin 850 mg b.i.d. for 6 weeks as a pilot study and within-patient comparison. Metformin decreased total and LDL-cholesterol (P less than 0.01), triglyceride (P less than 0.01), fasting plasma insulin (P less than 0.01) and C-peptide levels (P less than 0.02). Glucose disposal, an indicator of insulin action measured by means of the euglycaemic clamp technique, increased (P less than 0.001). Tissue plasminogen activator (t-PA) activity increased (P less than 0.02), and t-PA antigen decreased (P less than 0.01), whereas plasminogen activator inhibitor (PAI-1) and fibrinogen were unaffected by metformin treatment. Body weight remained unchanged. Withdrawal of metformin was associated with the return of both blood pressure and metabolism towards the initial levels. In conclusion, metformin treatment increased insulin action, lowered blood pressure, improved the metabolic risk factor profile and tended to increase the fibrinolytic activity in these mildly hypertensive subjects. These results support the view that insulin resistance plays a role in hypertension, and may open up a new field for the alleviation of abnormalities associated with cardiovascular disease.
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PMID:Treating insulin resistance in hypertension with metformin reduces both blood pressure and metabolic risk factors. 190 72

Metformin is a biguanide antidiabetic medication, that has been in use for over 30 years. Its mechanism of action, unknown until a few years ago, is now linked to an improved peripheral sensitivity to insulin, through a stimulated tissue glucose uptake by a transporter linked system. Interest in metformin has been revived by the recent observation of a specific activity of this agent on some of the major traits of the so called 'polymetabolic syndrome' (or 'syndrome X'), characterized by: insulin resistance, hypertriglyceridemia, hypertension and reduced fibrinolytic activity. Metformin, in studies examining one or more of these, has been shown, possibly through its peripheral insulin sensitizing mechanism, to correct most of the major symptoms characterizing this insulin resistance syndrome. Metformin, similarly to the other biguanide phenformin, has been rated as potentially dangerous, because of the possible induction of lactic acidosis, in some cases with a fatal outcome. Metformin is, however, associated with a very low incidence of lactic acidosis because, differently from phenformin, it does not undergo liver metabolism and, as a consequence, there are no high-risk groups, displaying an impaired metabolic handling. In this review, in addition to an overall evaluation of the more recent data on the mechanism of action and clinical use of metformin, a detailed clinical analysis of all published cases of lactic acidosis is provided. These data indicate that the risk in metformin use is negligible, provided that care is taken when prescribing the drug to patients with suspected clinical risks of lactic acidosis.
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PMID:Re-evaluation of a biguanide, metformin: mechanism of action and tolerability. 786 18

To determine the relationship between hyperinsulinemia and hypertension in spontaneously hypertensive rats (SHR), the antihyperglycemic agent metformin was administered to SHR and their Wistar-Kyoto (WKY) controls, and its effects on plasma insulin levels and blood pressure were examined. Five-week-old rats were started on oral metformin treatment (350 mg.kg-1.day-1, which was gradually increased to 500 mg.kg-1.day-1 over a 2-wk period). Metformin treatment caused sustained decreases in plasma insulin levels in the SHR (27.1 +/- 2.3 vs. untreated SHR 53.5 +/- 2.7 microU/ml, P < 0.001) without having any effect in the WKY (30.7 +/- 2.2 vs. untreated WKY 37.8 +/- 1.6 microU/ml, P > 0.05). The treatment did not affect the plasma glucose levels in any group. Metformin treatment also attenuated the increase in systolic blood pressure in the SHR (157 +/- 6.0 vs. untreated SHR 196 +/- 9.0 mmHg, P < 0.001) but had no effect in the WKY (134 +/- 3 vs. untreated WKY 136 +/- 4 mmHg, P > 0.05). Furthermore, raising plasma insulin levels in the metformin-treated SHR to levels that existed in the untreated SHR reversed the effect of metformin on blood pressure (189 +/- 3 vs. untreated SHR 208 +/- 5.0 mmHg, P > 0.05). These findings suggest that either hyperinsulinemia may contribute toward the increase in blood pressure in the SHR or that the underlying mechanism is closely associated with the expression of both these disorders.
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PMID:Metformin decreases plasma insulin levels and systolic blood pressure in spontaneously hypertensive rats. 794 68

In the present study, we examined the relationship between elevated insulin levels and hypertension in the fructose-hypertensive rat model, in which the rise in blood pressure is induced by feeding normal rats a fructose-enriched diet. Six-week-old Sprague-Dawley rats were divided into four experimental groups: control (C, n = 8), control metformin-treated (CT, n = 8), fructose-fed (F, n = 9) and fructose-fed, metformin-treated (FT, n = 10). Long-term oral metformin treatment (500 mg/kg/day) was begun in the CT and FT groups, and 1 week after the initiation of metformin treatment, the F and FT groups started receiving a 66% fructose diet. Metformin treatment prevented the increase in plasma insulin levels in the FT rats (FT, 32 +/- 4 microU; F, 51 +/- 7 microU-ml; P < .001) without any change in plasma glucose levels. Interestingly, metformin treatment also prevented the increase in systolic blood pressure in the FT group (FT, 143 +/- 2 mm Hg; F, 159 +/- 2 mm Hg; P < .001) but had no effect in the CT group (CT, 142 +/- 3 mm Hg; versus C, 141 +/- 2 mm Hg; P > .05). Restoration of plasma insulin levels in the FT group to levels that existed in the untreated F rats reversed the effect of metformin on blood pressure (FT plus insulin, 158 +/- 3 mm Hg; F, 160 +/- 3 mm Hg; P > .05). In conclusion, metformin prevents the hyperinsulinemia and hypertension that occur after feeding normal rats a fructose-enriched diet. Also, the antihypertensive effects of metformin can be reversed by raising the plasma insulin levels in the treated rats to those that exist in the untreated fructose-fed group, which suggests that hyperinsulinemia may contribute toward the increase in blood pressure in this model of experimental hypertension.
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PMID:Antihypertensive effects of metformin in fructose-fed hyperinsulinemic, hypertensive rats. 799 43

Hypertension is often associated with insulin resistance, and several chemically diverse agents that increase insulin sensitivity attenuate the development of experimental hypertension. We undertook the present study to determine whether attenuation of hypertension by pioglitazone, a thiazolidinedione derivative that increases insulin sensitivity without increasing insulin secretion, is specifically related to its effect on insulin-mediated glucose uptake. Pioglitazone administered daily by oral gavage (20 mg/kg per day) for 3 weeks attenuated the development of hypertension in both the Dahl salt-sensitive (DS) rat (an insulin-resistant model of hypertension) and the one-kidney, one clip rat (a model of hypertension not associated with insulin resistance). Based on euglycemic insulin clamp studies in conscious animals, the glucose clearance rate was increased (P < .05) in pioglitazone-treated DS rats (36 +/- 3 mg/kg per minute) compared with control DS rats (27 +/- 1 mg/kg per minute). However, pioglitazone did not affect the glucose clearance rate in one-kidney, one clip hypertensive rats. Metformin, an unrelated agent that also improves glucose tolerance, had no significant effect on blood pressure or glucose clearance rate in either DS or one-kidney, one clip rats. Thus, the hypotensive effect of pioglitazone is not invariably associated with its capacity to improve insulin-induced glucose utilization.
Hypertension 1994 Jul
PMID:Antihypertensive effect of pioglitazone is not invariably associated with increased insulin sensitivity. 802 Sep 98

Chronic treatment with the antihyperglycemic agent metformin prevents hypertension in spontaneously hypertensive rats. This effect has been ascribed to normalization of plasma insulin levels. However, whether metformin affects arterial pressure via changes in sympathetic nerve activity is unknown. Therefore, the objective of this study was to examine whether acute administration of metformin produces changes in mean arterial pressure, heart rate, or efferent renal sympathetic nerve activity in spontaneously hypertensive rats. Rats were anesthetized with alphaxalone-alphadolone (Saffan), paralyzed with pancuronium, and artificially ventilated. Intravenous administration of metformin (0, 1, 10, 100 mg/kg) produced dose-dependent reversible decreases in mean arterial pressure, heart rate, and efferent renal sympathetic nerve activity that were not affected by arterial or cardiopulmonary baroreceptor denervation, nitric oxide synthase inhibition by N(omega)-nitro-L-arginine methyl ester, or cyclooxygenase inhibition by indomethacin. Metformin given into the lateral cerebral ventricle (250, 500, 1000 microg) produced dose-dependent decreases in mean arterial pressure, heart rate, and efferent renal sympathetic nerve activity in doses that caused no changes when given intravenously. The sympathoinhibitory response to intracerebroventricular administration of metformin was not affected by alpha2-adrenoceptor blockade by intracerebroventricular yohimbine. We conclude that metformin has acute sympathoinhibitory effects (decreased arterial pressure, heart rate, and efferent renal sympathetic nerve activity) that are produced by a direct central nervous system site of action.
Hypertension 1996 Mar
PMID:Acute sympathoinhibitory actions of metformin in spontaneously hypertensive rats. 861 13

We have previously demonstrated that long-term metformin treatment prevents the development of hyperinsulinemia and hypertension in fructose-hypertensive (FH) rats; however, the exact nature of its antihypertensive effects remains elusive. Since hyperinsulinemia has been proposed to be a strong stimulus for norepinephrine (NE) release, the present study examined the effects of long-term metformin treatment (500 mg/kg/d for 10 weeks) on the reactivity of superior mesenteric arteries to NE in FH rats. Metformin treatment prevented the development of hyperinsulinemia and hypertension in FH rats. Mesenteric arteries from FH rats exhibited an increased cross-sectional area ([CSA] 0.45 +/- 0.07 mm2 v 0.32 +/- 0.05 in controls, P < .05), which was prevented by long-term metformin treatment (0.34 +/- 0.04 mm2, p > .05 v untreated FH). Interestingly, mesenteric arteries from metformin-treated fructose and control rats exhibited a reduction in maximum responsiveness to NE both with and without the endothelium. These data suggest that metformin directly reduces catecholamine constrictor responses in resistance arteries of rats, which may contribute to its antihypertensive effects in rats.
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PMID:Decreased vascular reactivity in metformin-treated fructose-hypertensive rats. 878 Dec 88

Noninsulin-dependent diabetes mellitus has historically been treated with diet therapy alone or the addition of an oral hypoglycemic agent such as a sulfonylurea, or the two in combination with insulin. Although these medical interventions lower blood glucose concentrations, they may also potentiate hyperinsulinism through increased serum insulin concentrations. Insulin resistance and hyperinsulinism are associated with cardiovascular risk factors such as hypertriglyceridemia, decreased high-density lipoprotein cholesterol levels, hypertension, and hyperglycemia, among others. Therefore, a desirable therapeutic alternative would lower blood glucose, not result in hyperinsulinism, and have beneficial effects on lipid profiles. Metformin is a biguanide antihyperglycemic agent that provides these effects. When administered to carefully selected patients and monitored appropriately metformin may prove to be valuable in the treatment of diabetes mellitus and in altering its cardiovascular sequelae.
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PMID:Metformin, a promising oral antihyperglycemic for the treatment of noninsulin-dependent diabetes mellitus. 901 66

Intravenous administration of the antihyperglycemic agent metformin decreases arterial pressure and sympathetic nerve activity (SNA). To test the hypothesis that metformin inhibits SNA by interrupting ganglionic neurotransmission, we compared the actions of intravenous administration of metformin and the ganglionic blocker trimethaphan on postganglionic renal and preganglionic adrenal sympathetic nerves in pentobarbital-anesthetized male Sprague-Dawley rats. Intravenous metformin elicited dose-dependent decreases in postganglionic renal SNA (1 mg/kg: 0 +/- 0%; 10 mg/kg: -20 +/- 4%; 100 mg/kg: -92 +/- 3%; n = 7). Conversely, only the maximal dose of metformin affected preganglionic adrenal SNA (100 mg/kg: delta adrenal SNA = -14 +/- 6%; n = 8). Ganglionic blockade with intravenous trimethaphan (5 mg/kg) produced a differential sympathoinhibitory response similar to the response observed after high-dose metformin (delta renal SNA = -100 +/- 3%; delta adrenal SNA = -17 +/- 7%; P < .001). Preganglionic renal neurons were electrically stimulated in the spinal cord, before and during the peak of the sympathoinhibitory response to intravenous metformin, and the magnitude of the stimulus-evoked increases in postganglionic renal SNA were compared. Metformin dose-dependently attenuated the magnitude of the increase in postganglionic renal SNA elicited by stimulation of the spinal cord (30 mg/kg: -23 +/- 8%; 90 mg/kg: -65 +/- 11%; 270 mg/kg: -91 +/- 8%; n = 6 per dose). We conclude that high-dose intravenous metformin interrupts ganglionic neurotransmission in renal nerves.
Hypertension 1997 May
PMID:Metformin inhibits ganglionic neurotransmission in renal nerves. 914 83


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