Barbagallo M

Quinapril reduces microalbuminuria in essential hypertensive and in diabetic hypertensive subjects

To investigate the metabolic and renal effects of the nonsulfhydryl, tissue-active ACE inhibitor quinapril in diabetes and in hypertension, we studied 30 essential hypertensives and 24 non-insulin-dependent (type II) diabetic (NIDDM) subjects with hypertension. Systolic and diastolic blood pressures, plasma glucose, and insulin responses to an oral glucose load (75 g), lipid profile, and urinary albumin excretion were evaluated before and after 8 weeks administration of quinapril (10 to 40 mg/day). Quinapril produced a significant and comparable reduction of arterial blood pressure in both groups. Mean arterial pressure decreased from 114.8 +/- 0.9 to 94.2 +/- 1.1 (-17.9 +/- 1.5%) in the essential hypertensive group and from 118.4 +/- 1.6 to 96.2 +/- 1.4 (-18.4 +/- 1.6%) in the diabetic hypertensive group. In both essential hypertensives and diabetic-hypertensive subjects with microalbuminuria, quinapril significantly and comparably reduced the urinary albumin excretion rate (UAE); UAE decreased from 32.5 +/- 5.5 micrograms/min to 14.7 +/- 3.7 micrograms/min (P < .05 v baseline) in the diabetic-hypertensive group and from 27.5 +/- 3.0 micrograms/min to 11.6 +/- 2.7 micrograms/min (P < .05 v baseline) in the essential hypertensives. Altogether, a direct correlation was found between the initial level of UAE and the UAE reduction after quinapril (delta UAE) (r = 0.706, p < .05). Insulin and glucose responses to an oral glucose tolerance test and the lipid profiles were not modified by quinapril treatment. The results confirm that quinapril is an effective antihypertensive agent that additionally reduces microalbuminuria in both hypertensive diabetics and in patients with essential hypertension, without altering insulin sensitivity and lipid profiles.

Protective Effects of Captopril Against Ischemic Stress: Role of Cellular Mg

Magnesium (Mg) deficiency enhances tissue sensitivity to ischemic damage, an effect reversed not only by Mg, but also by sulfhydryl (SH)-containing compounds. We therefore created an in vitro model of red blood cell ischemia to investigate whether the protective effects of these compounds might be related to effects on intracellular free Mg (Mg(i)) content. (31)P-nuclear magnetic resonance (NMR) spectroscopy was used to measure the high-energy metabolites ATP and 2,3-diphosphoglycerate (DPG) and Mg(i) and inorganic phosphate (P(i)) levels in erythrocytes before and for 6 hours after progressive oxygen depletion in the presence or absence of SH-compounds, including captopril, N-acetyl-L-cysteine (NAC), penicillamine, and N-(2-mercaptopropionyl)-glycine (MPG). Under basal aerobic conditions, captopril increased Mg(i) in a dose- and time-dependent fashion (174.5+/-5.3 to 217.1+/-5.1 micromol/L, P<0. 05 at 100 micromol/L, 60 minutes). The SH compounds NAC, penicillamine, and MPG but not the non-SH compound enalaprilat also significantly raised Mg(i) in erythrocytes (P<0.05). With oxygen deprivation, a consistent decrease occurred in both ATP and 2,3-DPG levels associated with a rise in P(i) and in the P(i)/2,3-DPG ratio used as an index of high-energy metabolite depletion. Captopril, compared with control, retarded the rise in P(i) and reduced the P(i)/2,3-DPG ratio (P<0.008 and P<0.025 at 4 and 6 hours, respectively). Furthermore, the higher the initial Mg(i) and the greater the captopril-induced rise in Mg(i), the greater the metabolite-protective effect (r=0.799 and r=0.823, respectively; P<0. 01 for both). Altogether, the data suggest that Mg influences the cellular response to ischemia and that the ability of SH compounds such as captopril to ameliorate ischemic injury may at least in part be attributable to the ability of such compounds to increase cytosolic free Mg levels.

Doxazosin lowers blood pressure and improves insulin responses to a glucose load with no changes in tyrosine kinase activity or insulin binding

alpha-Adrenergic blockers have shown favorable metabolic effects. We evaluated the glucose and insulin responses to a glucose load and lipid profiles in 36 diabetic hypertensive patients before and after 8 weeks of doxazosin administration. To evaluate insulin action at the cellular level, erythrocyte insulin binding and tyrosine kinase (TK) activity were measured in 12 of these patients. Systolic and diastolic blood pressures decreased significantly (P < .0001) after 8 weeks of doxazosin therapy. Doxazosin administration significantly reduced the integrated insulin response (area under the curve [AUC]-insulin: 6093 +/- 894 to 5260 +/- 807; P = .04) and the insulin/glucose index (I/G) at 90 and 120 min after a glucose load (at 90 min, 0.230 +/- 0.055 v 0.180 +/- 0.04, P < .05; at 120 min, 0.275 +/- 0.071 v 0.173 +/- 0.036, P < .05). HDL3 level increased from 31.1 +/- 1.5 mg% to 34 +/- 1.6 mg% (P < .05) after doxazosin. Erythrocyte insulin binding and tyrosine kinase activity were not significantly altered after doxazosin. No significant correlation was found between the insulin or glucose responses and the insulin receptor binding or tyrosine kinase activity before and after treatment.

Effect of aging on intracellular divalent cation metabolism: A link to the increased incidence of hypertension and non-insulin dependent diabetes mellitus in the elderly?

Aging is epidemiologically linked to an increased incidence of hypertension, impaired glucose tolerance and overt non-insulin dependent diabetes mellitus type II (NIDDM). The cellular basis underlying this clinical and epidemiological linkage, cytosolic free calcium (Ca(2+)(i)) and cytosolic free magnesium (Mg(2+)(i)) levels were investigated in elderly subjects and in subjects with essential hypertension (EH) and metabolic diseases. It has been observed that normal aging, as well as hypertension and NIDDM, is characterized by elevated Ca(2+)(i) and suppressed Mg(2+)(i) levels. Furthermore, the divalent ionic defect displayed in EH and NIDDM resembled the normal aging process, i.e., ionic levels in both young and elderly subjects with EH or NIDDM were indistinguishable from those in healthy elderly subjects. The ionic levels predict quantitatively also the extent of elevated blood pressure, and hyperinsulinemic response to oral glucose challenge. Altogether, we suggest that the missing link, responsible for the frequent and increasing clinical coexistence of hypertension, insulin resistance, impaired glucose tolerance, and NIDDM with age, may be ionic in nature, and intrinsic to the normal aging process in Western man.

Not All Fats Are Unhealthy

You don’t need to remove all fats from your diet because some of them actually help to promote good health. Fats are needed to build cell membranes, nerve covers, healthy hair, and skin, and to absorb some vitamins and other nutrients. They also prevent muscle breakage during fasting or food shortage. However, it’s clever to choose the healthier types of fats and enjoy them in moderation instead of picking truly bad fats, which should be avoided. Good fats comprise monounsaturated found in olive oil, avocados, and most nuts, and polyunsaturated, contained in vegetable oils and fatty fish. Trans fat, found in margarine, shortenings, snacks, and industrial baked products are the worst fats for you. They are byproducts of a chemical process and listed as “partially hydrogenated oil” in food labels. Saturated fats are present in various foods with highly heterogeneous health effects. The best bet to reduce harm from saturated fats is replacing them with good fats or other healthy foods and to avoid exchanging them with highly processed starches or added sugars.