Effective blood pressure treatment improves LDL-cholesterol susceptibility to oxidation in patients with essential hypertension.

OBJECTIVES: LDL-cholesterol particles from hypertensive patients exhibit enhanced susceptibility to in vitro oxidation, an abnormality thought to increase cardiovascular risk. We tested whether blood pressure (BP) normalization can reverse this abnormality. DESIGN: Double-blind, randomized pharmacological intervention trial. SETTING: Clinical research centre. Subjects. A total of 29 nondiabetic, normolipidaemic patients with essential hypertension (BP= 151 +/- 3/99 +/- 1 mmHg) and 11 normotensive controls (BP=125 +/- 3/85 +/- 1 mmHg) matched for gender, age, obesity, glucose tolerance and lipid profile. Intervention. Anti-hypertensive treatment for 3 months with a calcium-antagonist in randomized combination with either an ACE inhibitor or a beta-blocker. MAIN OUTCOME MEASURES: Lag phase of copper-induced LDL oxidation, cell-mediated (human umbilical vein endothelium) generation of malondialdehyde (MDA) by LDL and vitamin E content in LDL. RESULTS: At baseline in hypertensives versus controls, lag phase was shorter (89 +/- 3 vs. 107 +/- 6 min, P < 0.04), MDA generation was higher (5.8 +/- 0.1 vs. 5.1 +/- 0.2 nmol L(-1), P=0.002), and vitamin E was reduced (6.40 +/- 0.05 vs. 6.67 +/- 0.11 microg mg(-1), P=0.03). At 3 months, BP was normalized (124 +/- 3/81 +/- 1, P < 0.0001 vs. baseline, P=ns versus controls), lag phase was prolonged (to 98 +/- 3 min, P=0.0005), MDA generation was reduced (5.6 +/- 0.1 nmol L-1, P = 0.001), and vitamin E was increased (6.53 +/- 0.05 microg mg(-1), P=0.003), with no significant differences between the randomized groups. CONCLUSIONS: In nondiabetic, nonobese, normolipidaemic patients with essential hypertension, LDL susceptibility to copper- and cell-mediated oxidation is increased. BP normalization is associated with a significant improvement, but not a full reversal, of this abnormality.

Effect of physiological hyperinsulinemia on gluconeogenesis in nondiabetic subjects and in type 2 diabetic patients.

Gluconeogenesis (GNG) is enhanced in type 2 diabetes. In experimental animals, insulin at high doses decreases the incorporation of labeled GNG precursors into plasma glucose. Whether physiological hyperinsulinemia has any effect on total GNG in humans has not been determined. We combined the insulin clamp with the (2)H(2)O technique to measure total GNG in 33 subjects with type 2 diabetes (BMI 29.0 +/- 0.6 kg/m(2), fasting plasma glucose 8.1 +/- 0.3 mmol/l) and in 9 nondiabetic BMI-matched subjects after 16 h of fasting and after euglycemic hyperinsulinemia. A primed-constant infusion of 6,6-(2)H-glucose was used to monitor endogenous glucose output (EGO); insulin (40 mU. min(-1). m(-2)) was then infused while clamping plasma glucose for 2 h (at 5.8 +/- 0.1 and 4.9 +/- 0.2 mmol/l for diabetic and control subjects, respectively). In the fasting state, EGO averaged 15.2 +/- 0.4 micromol. min(-1). kg(-1)(ffm) (62% from GNG) in diabetic subjects and 12.2 +/- 0.7 micromol. min(-1). kg(-1)(ffm) (55% from GNG) in control subjects (P < 0.05 or less for both fluxes). Glycogenolysis (EGO - GNG) was similar in the two groups (P = NS). During the last 40 min of the clamp, both EGO and GNG were significantly (P < 0.01 or less, compared with fasting) inhibited (EGO 7.1 +/- 0.9 and 3.6 +/- 0.5 and GNG 7.9 +/- 0.5 and 4.5 +/- 1.0 respectively) but remained significantly (P < 0.05) higher in diabetic subjects, whereas glycogenolysis was suppressed completely and equally in both groups. During hyperinsulinemia, GNG micromol. min(-1). kg(-1)(ffm) in diabetic and control subjects, was reciprocally related to plasma glucose clearance. In conclusion, physiological hyperinsulinemia suppresses GNG by approximately 20%, while completely blocking glycogenolysis. Resistance of GNG (to insulin suppression) and resistance of glucose uptake (to insulin stimulation) are coupled phenomena. In type 2 diabetes, the excess GNG of the fasting state is carried over to the insulinized state, thereby contributing to glucose overproduction under both conditions.

Metabolic effects of glucose-insulin infusions: myocardium and whole body.

In target organs, insulin switches substrate utilization from free fatty acids to glucose, a change that: (i) is oxygen-efficient; (ii) repletes glycogen stores; (iii) removes potentially toxic fatty acids; and (iv) restores intracellular potassium. During or after an ischaemic challenge, the insulin metabolic mode should protect cellular functions provided that insulin can reach the ischaemic tissue. Insulin, however, also exerts non-metabolic effects, such as membrane hyperpolarization, the stimulation of adrenergic activity, and inhibition of parasympathetic tone, which may counter its beneficial metabolic actions. The net balance between the favourable and unfavourable effects of insulin on ischaemic tissues depends on: (i) the dose-response of the various effects; (ii) the presence of insulin resistance; (iii) the coexistence of hyperglycaemia; and (iv) the stage of ischaemic tissue damage. At present, a role for glucose-insulin-potassium infusions in clinical practice seems to be clearly established in the case of diabetic patients with acute coronary syndromes, and in patients undergoing urgent or elective cardiac surgery. Its role as an adjunctive therapy in the management of myocardial infarction in non-diabetic individuals has been tested in several clinical trials; however, the evidence emerging from them is inconclusive.

Evidence that acute insulin administration enhances LDL cholesterol susceptibility to oxidation in healthy humans.

Increased free radical production and hyperinsulinemia are thought to play a role in experimental and human atherosclerosis, but the relation between the 2 abnormalities has not been studied. In 23 healthy volunteers, we measured the susceptibility of circulating low-density lipoprotein (LDL) cholesterol particles to in vitro copper sulfate oxidation (measured as the lag phase) and cell-mediated oxidative modification (measured as malondialdehyde generation in LDL during incubation with human umbilical vein endothelial cells), as well as the vitamin E content of LDL cholesterol at baseline and after 2 hours of physiological hyperinsulinemia (euglycemic insulin clamp). The lag time of LDL oxidation decreased from control values of 108+/-3 and 107+/-3 minutes (at baseline and after 2 hours of saline infusion) to 101+/-3 minutes after 2 hours of clamping (P<0.0001). At corresponding times, cell-mediated malondialdehyde generation in LDL rose from 4.96+/-0.11 and 4.98+/-0.10 to 5.28+/-0.10 nmol/L (P=0. 0006), whereas the LDL vitamin E content decreased from 6.78+/-0.06 and 6.77+/-0.06 to 6.64+/-0.06 microg/mg (P<0.04). The insulin-induced shortening of the lag phase was directly related to the decrement of vitamin E in LDL; furthermore, in subjects with higher baseline serum triglyceride levels, insulin induced a greater shortening of the lag phase than in subjects with low baseline triglycerides. We conclude that in healthy humans acute physiological hyperinsulinemia enhances the oxidative susceptibility of LDL cholesterol particles. This effect may have pathogenic significance for atherogenesis in insulin resistant states.

Survival after massive (>2000) Africanized honeybee stings.

We report the clinical case of a man who survived a massive attack of Africanized bees (>2000 bee stings). The man experienced anaphylactic shock and multisystem organ failure (neurologic, hepatic, renal, and hematologic failure). He was treated with administration of dopamine hydrochloride, antihistaminic agents, corticosteroids, fluid and electrolyte replenishment, peritoneal dialysis, and plasmapheresis. No sequelae have been observed during follow-up.

Pyoderma gangrenosum and extensive caval thrombosis associated with the antiphospholipid syndrome--a case report.

Pyoderma gangrenosum is a rare cutaneous disorder frequently associated with systemic diseases. The authors report the case of a 28-year-old man with pyoderma gangrenosum and inferior cava vein syndrome due to thrombosis. The search for pyoderma gangrenosum-associated conditions (gastrointestinal, rheumatic, neoplasic, and infectious diseases) was negative. A prolonged partial thromboplastin time and a positive test for circulating anticardiolipin antibodies strongly suggested the diagnosis of the antiphospholipid syndrome. There are reports of at least three other cases of pyoderma gangrenosum associated with the antiphospholipid syndrome. This clinical case adds further evidence to the possible link between these disorders and warrants a search for anticardiolipin antibodies in patients with pyoderma gangrenosum.

Vasodilation with sodium nitroprusside does not improve insulin action in essential hypertension.

The vasodilation induced by systemic insulin infusion is mediated by nitric oxide and is impaired both in obese subjects and patients with essential hypertension. Whether this vascular defect explains the metabolic resistance to insulin action is uncertain. In 8 overweight male patients with essential hypertension, we used the double forearm (ie, infused versus control) technique, combined with the euglycemic hyperinsulinemic clamp, to test whether sustained vasodilation (induced by intra-arterial sodium nitroprusside infusion) improves insulin-mediated glucose uptake. During the clamp, whole-body glucose disposal rose to 24.4+/-2.9 micromol x min(-1) x kg(-1). Forearm blood flow in the control forearm was stable (3.1+/-0.4 versus 2.9+/-0.3 mL x min[-1] x dL[-1]), while in the infused forearm it increased from 3.4+/-0.5 to 10.6+/-1.3 mL x min(-1) x dL(-1) in response to sodium nitroprusside. During insulin administration, tissue glucose extraction rose from 2+/-1% to 21+/-4% (P<.001) in the control forearm and from 2+/-1% to 8+/-3% in the infused forearm (P<.02 versus baseline for both); the calculated net glucose uptake reached similar plateaus in the two forearms (3.5+/-0.7 versus 3.7+/-0.6 micromol x min(-1) x kg(-1), control versus infused, P=.6). We conclude that in overweight male patients with essential hypertension, increasing forearm perfusion with sodium nitroprusside does not attenuate the insulin resistance of forearm tissues.

Metabolic profile and insulin sensitivity in healthy young Mexicans with a strong family history of non-insulin-dependent diabetes mellitus in the paternal branch.

The objective was to identify early metabolic defects and insulin sensitivity in a group of healthy young Mexicans with a family history of NIDDM in first and second degree on the paternal branch. The design was a cross-sectional study, and the setting was a hospital and a school of medicine in Guadalajara, Jalisco, Mexico. The subjects were 20 healthy, non-obese, young (age 19-20 years), born in Mexico, with family history of NIDDM in first and second degree in the paternal branch, and 20 controls. Measurements were serum values of creatinin, uric acid, total cholesterol, high-density lipoprotein cholesterol, triglycerides, glucose, and insulin, insulin tolerance test, glucose/insulin ratio, LDL cholesterol, VLDL cholesterol, total cholesterol/HDL cholesterol ratio and LDL cholesterol/HDL cholesterol ratio. In terms of results, only the total cholesterol was slightly, although significantly (p = 0.05) higher in probands (4.3 +/- 0.5 mmol/L) than in control subjects (3.9 +/- 0.5 mmol/L). In conclusion, healthy young Mexicans with a strong family history of NIDDM in the paternal branch were not different in insulin sensitivity from those without family history of NIDDM, and only showed a slight increase in serum total cholesterol.

Insulin sensitivity, vascular reactivity, and clamp-induced vasodilatation in essential hypertension.

BACKGROUND: Insulin resistance and vascular abnormalities have both been described in patients with essential hypertension. Whether these defects are associated with one another in the same individual has not been established. METHODS AND RESULTS: Whole-body insulin sensitivity (by the insulin clamp technique), forearm minimal vascular resistances, and the dose-response curve to acetylcholine, sodium-nitroprusside, and norepinephrine were measured in a group of 29 male patients with untreated essential hypertension. When the patients were divided into tertiles according to their level of insulin sensitivity, resistant and sensitive hypertensives were matched on several potential confounders of insulin action and vascular function. These subgroups showed similar minimal vascular resistances (2.5+/-0.2 versus 3.2+/-0.6 mm Hg per mL x min(-1) x dL(-1)) and superimposable responses to graded intraarterial infusions of acetylcholine, sodium-nitroprusside, and norepinephrine. No correlation was found between the vascular parameters (slope of the curve or maximal response) and insulin-mediated glucose uptake in the whole group. During the clamp, insulin sensitive patients tended to have greater increments in forearm blood flow when compared to their insulin resistant counterparts (+53+/-21 versus +9+/-7%, P=.06); in the whole group, clamp-induced vasodilatation was weakly related to insulin-mediated glucose uptake (r=.44, P<.02) as well as to the slope of the acetylcholine dose-response curve (r=.40, P<.04). Together, these two responses explained 30% (multiple r=.55, P<.01) of the variability in insulin-induced vasodilatation. CONCLUSIONS: Metabolic insulin resistance in essential hypertension is not associated with abnormalities in vascular structure, acetylcholine or nitroprusside-induced vasodilatation, or vascular adrenergic reactivity. Degree of insulin sensitivity and acetylcholine sensitivity explain a small portion of the variability of the clamp-induced vasodilatation in hypertensive patients.

Renal effects of insulin in man.

We review some of the effects that insulin exerts on glomerular and tubular functions. In healthy subjects, insulin has little or no effect on renal hemodynamics, glomerular filtration rate, or permeability to albumin. In patients with noninsulin-dependent diabetes, hyperinsulinemia selectively increases urinary albumin excretion. In vivo, euglycemic hyperinsulinemia is associated with reduced urinary sodium excretion both under conditions of forced and normal diuresis. Whether the principal site of this action is the proximal or distal tubule remains somewhat controversial. The effect, however, is not mediated by insulin-induced hypokalemia and antikaliuresis, as it is still observed when plasma potassium concentrations and urinary potassium excretion are maintained. Hyperglycemia potentiates insulin antinatriuresis through an effect on the proximal tubule (sodium-glucose cotransport). Insulin antinatriuresis is accompanied by a reduction in the urinary excretion of uric acid. Both the antinatriuretic and antiuricosuric effect of insulin are preserved in states of insulin resistance of glucose metabolism (obesity, diabetes, essential hypertension). Thus, in insulin resistant individuals compensatory hyperinsulinemia imposes a chronic antinatriuretic and antiuricosuric pressure on the kidney. This may provide an explantation for the clustering of insulin resistance with hypertension and hyperuricemia.

Effect of insulin on systemic and renal handling of albumin in nondiabetic and NIDDM subjects.

Insulin resistance and hyperinsulinemia cluster with microalbuminuria in both diabetic and nondiabetic subjects, but the mechanism underlying this association is unknown. To test the hypothesis that insulin influences protein permeability, we measured the albumin transcapillary escape rate (TER) by the (131)I-labeled albumin technique in 12 healthy volunteers and 12 normoalbuminuric NIDDM patients (fasting plasma glucose, 10.9 +/- 1.3 mmol/l) during 4 h of isoglycemia with high (1.1 mU x min(-1) x kg(-1)) or, on a different day, low (0.1 mU x min(-1) x kg(-1)) insulin infusion. In both patients and control subjects, high insulin was associated with a 7% decrease in blood volume (P = 0.006) and a 6% decrease in diastolic blood pressure (P < 0.02), these two changes being related to one another (r = 0.56, P < 0.01). Basal albumin TER was similar in patients (8.4 +/- 0.5% x h(-1)) and control subjects (7.7 +/- 0.7% x h(-1)) and was not significantly changed by high insulin in either group (patients vs. control subjects, 7.3 +/- 0.9 vs. 6.2 +/- 0.4% x h(-1); NS vs. low insulin). In contrast, high insulin increased renal albumin excretion (from 3.6 +/- 0.8 to 5.4 +/- 1.1 microg/min, P < 0.01) and clearance rate (0.09 +/- 0.02 to 0.13 +/- 0.03 microl/min, P < 0.001) in patients but not in control subjects. To localize the effect of insulin along the nephron, we measured the urinary excretion of N-acetyl-beta-D-glucosaminidase (beta-NAG), released by the proximal tubule; retinol-binding protein (RBP), reabsorbed by the proximal tubule; and Tamm-Horsfall protein (THP) and epidermal growth factor (EGF), both secreted by the distal tubule. For both beta-NAG and RBP, but not EGF or THP, insulin enhanced urinary excretion (diabetics vs. controls: beta-NAG, 0.48 vs. -0.15 microU/min [P = 0.03]; RBP, 78 vs. -32 ng/min [P = 0.05]). In conclusion, physiological hyperinsulinemia does not affect systemic albumin permeability in healthy subjects or normoalbuminuric NIDDM patients. In contrast, in NIDDM patients, but not in healthy subjects, insulin increases the urinary excretion of albumin and protein markers of proximal tubular function. The significance of this finding for the pathogenesis of diabetic nephropathy remains to be established.

Delta-aminolevulinic acid dehydratase and zinc protoporphyrin in very low lead-exposed pets: a community study.

Markers of lead intoxication have been developed based on their capacity to identify lead intoxication at the preclinical, ie biochemical stage of manifestation. However, little information on these markers is available under conditions of low lead exposure. This prompted us to conduct a community-based study to determine the usefulness of theta-aminolevulinic acid dehydratase (ALAD) and zinc protoporphyrin (ZnPP) in conditions of low lead environmental exposure by studying the relationships between low blood lead levels, ALAD and ZnPP in a large group of healthy dogs living in an Italian urban area. The study population consisted of 79 dogs. Each sample was tested for ALAD, lead and ZnPP and for complete blood count, hemoglobin, AST, ALT, and urea values. A weak inverse relationship between ALAD and ZnPP was found. An inverse relationship between ALAD and lead concentrations was found in the whole group (p < 0.0005). This relationship remained significant when selecting the values falling between 2 standard deviations of the mean blood lead concentrations of the population below the "concerned lead levels" (< 10 mg/dl; p = 0.0005). There was no relationship between whole blood ZnPP concentrations and whole blood lead levels. The sensitivity and specificity of ALAD measurements, calculated by using the 2 x 2 contingency table with respect to blood lead concentrations, were of poor predictive diagnostic value.

Renovascular hypertension and insulin sensitivity.

We tested the hypothesis that the status of the renin-angiotensin-aldosterone system affects insulin sensitivity. Insulin sensitivity (by the euglycaemic insulin clamp technique) was measured in eight patients with angiographically proven renovascular hypertension and in eight normotensive subjects matched for age, gender, body mass index and glucose tolerance. In the patients, insulin sensitivity was measured both at baseline and following 7 days of ACE inhibition. Following glucose ingestion, patients and controls showed similar insulin and glucose responses. Insulin infusion (7 pmol min-1 kg-1) promoted similar glucose utilization in the hypertensives and normotensives: 24.8 +/- 2.3 vs. 26.0 +/- 3.0 mumol min-1 kg-1 respectively. One week of ACE inhibition caused a 20 +/- 4 mmHg decrease in mean blood pressure and a 20 +/- 6% decrease in peripheral vascular resistance. Plasma angiotensin II concentrations dropped from 24.6 +/- 6.3 to 13.5 +/-5.0 pg mL-1 (P < 0.05) and plasma aldosterone from 17 +/- 4 to 9 +/- 2 ng dL-1 (P < 0.05), and plasma renin activity doubled (from 1.6 +/- 0.3 to 3.4 +/- 1.7 ng mL-1 h-1, P < 0.02). Nevertheless, insulin sensitivity was unchanged (before, 24.8 +/- 2.3; after 25.8 +/- 2.2 mumol min-1 kg-1, P = Ns). During insulin infusion, forearm blood flow did not change from baseline in either set of studies. Also, the antinatriuretic (before, -26 +/- 18; after, -22 +/- 14%) and antikaliuretic (before: -36 +/- 13%, after -39 +/- 11%) action of the hormone was unaffected by the therapy. In conclusion, renovascular hypertension is not associated with insulin resistance. Furthermore, a selective, drastic reduction of the renin-angiotensin-aldosterone system activity and vascular tone does not alter insulin action on glucose and electrolyte metabolism.

Hyperinsulinemia in glucose-tolerant women with preeclampsia. A controlled study.

Essential hypertension is associated with insulin resistance and hyperinsulinemia. To assess whether hyperinsulinemia is also present in hypertensive disease induced by pregnancy, we studied the plasma glucose and insulin responses to 50 g of oral glucose in 10 women with definite, severe preeclampsia but normal glucose tolerance, and compared them with the responses observed in a well-matched control group of healthy pregnant women. Fasting plasma glucose concentrations were similar in healthy and preeclamptic pregnant mothers (4.1 +/- 0.4 mmol/L v 4.5 +/- 0.4 mmol/L, respectively, P = NS). Similar plasma glucose levels were also observed after glucose ingestion (5.5 +/- 0.3 mmol/L v 6.2 +/- 0.3 mmol/L in healthy and preeclamptic women, respectively P = NS). In contrast, fasting plasma insulin concentrations in the preeclamptic women were significantly higher than in normal pregnant mothers (175 +/- 29 pmol/L v 101 +/- 11 pmol/L, P < .05). Postload plasma insulin concentrations were nearly fourfold higher in the preeclamptic group as compared with the control group (1162 +/- 70 pmol/L v 366 +/- 39 pmol/L, P < .01). We conclude that preeclampsia is associated with marked hyperinsulinemia both in the fasting state and after oral glucose ingestion, suggesting that insulin resistance may play a role in pregnancy-induced hypertension.

Insulin resistance in microalbuminuric hypertension. Sites and mechanisms.

Microalbuminuria in patients with essential hypertension is a marker of incipient glomerular dysfunction and clusters with lipid and hemodynamic abnormalities. Recent evidence has shown that hypertensive patients with microalbuminuria have a hyperinsulinemic response to oral glucose, suggesting the presence of insulin resistance. To directly test this possibility we studied insulin action in two accurately matched groups (n = 10 each) of hypertensive patients with or without microalbuminuria (14 +/- 2 versus 52 +/- 7 mg/24 h-1, mean of three 24-hour collections). In response to glucose ingestion microalbuminuric patients showed slight hyperglycemia (area under the curve, 928 +/- 43 versus 784 +/-19 nmol/L-1/2h-1, P < .02) and a marked hyperinsulinemia (26.8 +/- 3.3 versus 49.8 +/- 3.7 nmol/L-1/2h-1, P < 0.01). Basal arterial blood pressure, heart rate, and forearm blood flow were similar in the two groups and did not change significantly during a 2-hour euglycemic insulin clamp. Insulin-stimulated wholebody glucose uptake was 25% lower in microalbuminuric patients (33.5 +/- 2.5 versus 25.2 +/- 2.1 mumol/min-1/kg-1, P < .02). This difference was entirely due to a 40% reduction in glycogen synthesis (12.9 +/- 1.8 versus 21.3 +/- 3.2 mumol/min-1/kg-1, P < .05) as glucose oxidation was similarly stimulated in the two groups. In contrast there was no difference in the ability of insulin to suppress hepatic glucose production (by approximately 100% at the end of the clamp), to decrease fractional sodium and potassium excretions (by 35%), to lower circulating free fatty acids (by 80%), and to reduce plasma potassium concentrations (by 10%).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of insulin on uric acid excretion in humans.

Although hyperuricemia is a frequent finding in insulin-resistant states, insulin's effect on renal uric acid (UA) handling is not known. In 20 healthy volunteers, diastolic blood pressure, body weight, and fasting plasma insulin were positively (and age was negatively) related to fasting plasma UA concentrations, together accounting for 53% of their variability. During an insulin clamp, urine flow was lower than during fasting conditions (1.01 +/- 0.12 vs. 1.56 +/- 0.32 ml/min, P = 0.04), whereas creatinine clearance was unchanged (129 +/- 7 and 131 +/- 9 ml/min, P = not significant). Hyperinsulinemia did not alter serum UA concentrations (303 +/- 13 vs. 304 +/- 12 microM) but caused a significant decrease in urinary UA excretion [whether expressed as absolute excretion rate (1.66 +/- 0.21 vs. 2.12 +/- 0.23 mumol/min, P = 0.03), clearance rate (5.6 +/- 0.8 vs. 7.3 +/- 0.8 ml/min, P = 0.03), or fractional excretion (4.48 +/- 0.80 ml/min vs. 6.06 +/- 0.64%, P < 0.03)]. Hyperinsulinemia was also associated with a 30% (P < 0.001) fall in urine Na excretion. Fractional UA excretion was related to Na fractional excretion under basal conditions (r = 0.59, P < 0.01) and during the insulin period (r = 0.53, P < 0.02). Furthermore, the insulin-induced changes in fractional UA and Na excretion correlated with one another (r = 0.66, P < 0.001). Physiological hyperinsulinemia acutely reduces urinary UA and Na excretion in a coupled fashion.

Relationship between insulin release, antinatriuresis and hypokalaemia after glucose ingestion in normal and hypertensive man.

1. Insulin simultaneously causes hypokalaemia and antinatriuresis, and it has been suggested that the two effects are tightly coupled. Whether these actions are preserved in patients with essential hypertension is not known. 2. Eight hypertensive patients and eight normotensive control subjects were studied before and after the ingestion of 75 g of glucose. Despite similar glycaemic profiles, the patients showed a hyperinsulinaemic response incremental area 49 +/- 8 versus 27 +/- 6 nmol l-1 3 h, P < 0.04) but a blunted hypokalaemic response (-7 +/- 1 versus -16 +/- 1%, P < 0.001). Both absolute and fractional urinary excretion of sodium and potassium were significantly decreased during glucose-induced hyperinsulinaemia in hypertensive patients as well as in normotensive subjects (P < 0.05 for all changes). 3. To test whether hypokalaemia is required for insulin-induced antinatriuresis, each hypertensive patient received another oral glucose load during which enough potassium chloride was given to clamp the plasma potassium concentration at baseline. Under these conditions, significant insulin-induced antinatriuresis still occurred. In addition, whereas the glycaemic profile was superimposable, the response of the plasma insulin concentration was significantly greater with than without maintenance of the plasma potassium concentration (total area 79 +/- 14 versus 63 +/- 8 nmol l-1 3 h, P < 0.04). 4. We conclude that (a) insulin causes antinatriuresis, antikaliuresis and hypokalaemia under physiological conditions; (b) in hyperinsulinaemic (insulin-resistant) patients with essential hypertension, the antinatriuretic action of insulin is quantitatively preserved; and (c) clamping plasma potassium levels prevents insulin-induced antikaliuresis but not antinatriuresis, and potentiates the insulin secretory response to glucose.