Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the hypothesis that insulin is a causal and independent risk factor for blood pressure elevation in humans by comparing pre- and post-operative blood pressure values of 34 consecutive patients with histologically-confirmed diagnosis of insulinoma and 34 age- and sex-matched control patients. In patients with insulinoma hypoglycaemic symptoms were present for 18 (9-36) months. (Values are given as median and 95% confidence interval or mean and SD). After removal of insulinoma fasting plasma insulin levels decreased from 22 (16-28) mU/l to 11 (6-20) mU/l (p less than 0.003) and minimal fasting plasma glucose concentrations increased from 2.5 (2.0-3.0) to 4.4 (4.2-5.7) mmol/l (p less than 0.002) while blood pressure values remained unchanged. Body mass index before operation was comparable between the groups: 25.5 (5.4) kg/m2 in insulinoma patients and 24.8 (4.7) kg/m2 in control subjects. Pre-operative and post-operative blood pressure values did not differ between the groups, being (systolic/diastolic) 133 (18)/82 (9) mm Hg in insulinoma patients and 128 (15)/78 (10) mm Hg in control subjects before and 129 (19)/80 (10) mm Hg and 125 (11)/76 (7) after surgery. Chronic hyperinsulinaemia in patients with insulinoma is not associated with a detectable elevation of blood pressure values. Correction of hyperinsulinaemia after surgery for insulinoma does not result in blood pressure changes. These results argue against the hypothesis that insulin is an independent causal factor in the development of essential hypertension in humans.
 ...
PMID:Hyperinsulinaemia is not linked with blood pressure elevation in patients with insulinoma. 164 43

Essential hypertension is often accompanied by metabolic abnormalities which commonly include hyperinsulinemia/insulin resistance. Even in the absence of these metabolic disorders, high blood pressure tends to be associated with insulin resistance. These observations raise two orders of questions: 1) whether hyperinsulinemia and insulin resistance are simply innocent bystanders or are causally involved in the initiation and/or promotion of hypertension; 2) whether blood pressure elevation is eventually caused by excess of insulin or whether it is a manifestation of the complex metabolic state responsible for insulin resistance. The purpose of this paper is to survey the clinical, epidemiological and experimental data that have led to the above generalizations and to address the potential significance of this coexistence. First, it could be argued that the relationship between high blood pressure and the associated metabolic defects is incidental. In this case, insulin resistance and hypertension may represent two independent consequences of a same metabolic disorder. On the other hand, there is evidence that suggests that insulin resistance (by itself or by insulin) may play a role in the etiology and/or the clinical course of hypertension. Although insulin has complex actions on the circulation (including a vasodilator effect), plausible mechanisms by which insulin might raise blood pressure include stimulation of the sympathetic nervous system, alteration of ion transport kinetics, increase of renal sodium retention and stimulation of vascular smooth cells growth. The pathways that could link insulin resistance, through hyperinsulinemia, with essential hypertension are based on the concept that a defect of insulin action on glucose utilization, does not imply that all other effects of insulin are equally blunted. However, in patients with insulinoma, hypertension has not been associated, and the acute administration of insulin does not cause an increase in blood pressure. It is also possible, on the contrary, that hypertension may be the cause of insulin resistance, but in various forms of secondary hypertension, impaired insulin sensitivity has not been found. It is probable that insulin resistance may represent, in a subgroup of individuals characterized by genetic predisposition (ethnicity, familiarity, etc.), simply a marker for susceptibility to hypertension. Hyperinsulinemia, in these subjects, may directly contribute to a raise in blood pressure by several mechanisms. In conclusion, despite the clinical importance of this association the nature of the relationship between insulin resistance and blood pressure remains obscure. Since hypertension does not develop in all insulin resistant subjects and hyperinsulinemia does not always cause a raise in blood pressure, the relationship must be modulated by other genetic or environmental factors.
 ...
PMID:[Hyperinsulinism/insulin resistance: cause, effect or marker of essential arterial hypertension?]. 764 26

Hypertension and diabetes mellitus are common chronic conditions which frequently coexist. Diabetic nephropathy is a major cause of elevated blood pressure in patients with insulin-dependent diabetes mellitus (IDDM). Diabetic nephropathy, arterial sclerosis, obesity and association of essential hypertension can be the causes of hypertension in patients with non-insulin-dependent diabetes mellitus (NIDDM). Ambulatory blood pressure monitoring has revealed that the nocturnal fall of blood pressure is blunted in patients with diabetic nephropathy. A blunted diurnal blood pressure variation is seen in microalbuminuric diabetic patients and even in some normoalbuminuric patients. Accumulating data suggest that normalisation of blood pressure in hypertensive IDDM patients is most important to minimise the loss of kidney function. Angiotensin converting enzyme (ACE) inhibitors have been reported to be effective in postponing the development of nephropathy and in slowing its progression. Whether only ACE inhibitors have such beneficial renal effects on diabetic nephropathy is under discussion. While many studies have suggested that insulin resistance and hyperinsulinaemia are related to an elevated blood pressure in hypertensive patients, there does not seem to be enough evidence to prove that insulin per se can raise blood pressure in humans. Neither an insulin infusion within a physiological range nor sustained hyperinsulinaemia and insulin resistance (e.g. patients with insulinoma, cystic ovary syndrome) have been associated with an elevated blood pressure. Insulin resistance in some hypertensive patients may be a consequence of a decreased blood flow due to an increased peripheral resistance. Preliminary evidence suggests that low birth weight or impaired fetal growth is related to hypertension and NIDDM. Familial clustering of diabetic nephropathy suggests the contribution of genetic susceptibility and/or environmental inheritance. The frequent association of nephropathy with hypertension has led to research on the genes related to hypertension (ACE, angiotensinogen). Nevertheless, to date no reliable and clinically useful genetic marker has been found. Attempts to correct the metabolic abnormalities derived from diabetes are a new topic in the treatment of diabetic nephropathy. The effects of HMG CoA reductase inhibitors (antihypercholesterolaemic drugs), aldose reductase inhibitors (inhibitors of the polyol pathway) and glycation inhibitors (inhibitors of formation of advanced glycosylation end-products) on diabetic nephropathy have been evaluated in animal studies and in some clinical trials. Thus far, results with HMG CoA reductase and aldose reductase inhibitors have been somewhat conflicting. The potential therapeutic role of glycation inhibition in the treatment of diabetes deserves further study.
 ...
PMID:Diabetic nephropathy. Its relationship to hypertension and means of pharmacological intervention. 925 79