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T A Kotchen

Publications and source records attributed to T A Kotchen.

At least 37 records · Page 2Linked to original sources
PubMed1997

Increasing insulin sensitivity lowers blood pressure in the fructose-fed rat.

In the rat, simple carbohydrate feeding induces insulin resistance, and insulin resistance is associated with impaired endothelium dependent vasodilation. To determine if increasing insulin sensitivity corrects this defect of endothelial function, we evaluated the effects of an insulin-sensitizing agent, pioglitazone, on arterial pressure and in vitro vascular reactivity in three groups of Sprague Dawley rats: 1) control; 2) 60% fructose diet for 4 weeks; 3) 60% fructose diet plus pioglitazone (20 mg/kg daily, by oral gavage). Direct mean arterial pressure did not differ in Groups 1 (120 mm Hg +/- 2) and 2 (121 +/- 2) and was lower (P < .05) in Group 3 (112 +/- 2). In vitro uptake of tritiated glucose by adipocytes in response to insulin was reduced (P < .05) by fructose and increased (P < .01) by pioglitazone. In strips of thoracic aorta, norepinephrine-induced vasoconstriction and nitroprusside induced vasodilation did not differ among groups. However, in response to graded dose of acetylcholine, vasodilation was reduced (P < .05) by fructose; this was normalized by pioglitazone. In all groups, N(G)-nitro-L-arginine methyl ester (L-NAME) completely blocked acetylcholine-induced vasodilation. Thus, pioglitazone increased insulin sensitivity, lowered blood pressure, and normalized acetylcholine-induced vasodilation in insulin resistant, fructose-fed rats. Increasing insulin sensitivity may lower arterial pressure by augmenting endothelium dependent vasodilation.

Acetylcholine↗
PubMed1997

Dietary sodium and blood pressure: interactions with other nutrients.

This paper reviews the evidence that salt sensitivity of blood pressure is related both to the anion ingested with sodium as well as to other components of the diet. In several experimental models of salt-sensitive hypertension and in humans, blood pressure is not increased by a high sodium intake provided with anions other than chloride. Salt-induced increase of blood pressure depends on the concomitant ingestion of both sodium and chloride. Both epidemiologic and clinical evidence suggest that sodium chloride-induced increases of blood pressure are augmented by diets deficient in potassium or calcium. In experimental animals, a high intake of simple carbohydrates also augments sodium chloride sensitivity of blood pressure. These observations indicate that the effect of dietary sodium on blood pressure is modulated by other components of the diet.

Animals↗
PubMed1996

Attenuation of experimental hypertension by dietary linoleic acid is model dependent.

OBJECTIVE: The purpose of this study was to evaluate the interaction of a linoleic acid enriched diet with NaCl on the development of hypertension in Dahl salt sensitive (Dahl-S) rats and in two-kidney, one-clip Sprague Dawley rats. METHODS: In both experimental models, separate groups of animals were fed either linoleic acid enriched (provided as safflower oil) or control (containing coconut oil) diets for 5 weeks. Diets were further subdivided on the basis of either a low NaCl (0.3%) or a high NaCl (3.0%) content. Tail systolic blood pressure, direct mean intra-arterial pressure, and cardiac output were measured in chronically instrumented, conscious rats. RESULTS: In Dahl-S, on both NaCl intakes, and in two-kidney, one-clip rats on a high NaCl diet, safflower oil had no effect on arterial pressure. In contrast, in two-kidney, one-clip rats fed the low NaCl diet, both indirect tail systolic blood pressures and direct mean arterial pressure were lower (p<0.01) in animals on the linoleic acid enriched diet; total peripheral resistance was also decreased (p<0.01). CONCLUSION: Safflower oil has a hypotensive effect only in the two-kidney, one-clip rat on a low NaCl, but not on a high NaCl intake, and not in Dahl-S rats. Additional studies are required to identify the mechanism(s) for the hypotensive effect of safflower oil and to define the relationship of this animal study to human hypertension.

Animals↗
PubMed1996

Insulin and hypertensive cardiovascular disease.

Resistance to insulin-stimulated glucose uptake is associated with several cardiovascular disease risk factors, including hypertension, dyslipidemia, and alterations of the blood clotting cascade that accentuate thrombosis. This constellation of risk factors may be recognized at young ages and is at least in part heritable. Recognition of this syndrome dictates that preventive and therapeutic strategies should address overall cardiovascular disease risk. In patients with hypertension or diabetes, additional clinical trials are required to identify those interventions that will most effectively reduce not only overall risk but also definitive cardiovascular disease endpoints.

Adult↗
PubMed1996

Effect of pioglitazone on vascular reactivity in vivo and in vitro.

Pioglitazone (a thiazolidinedione derivative) increases insulin sensitivity and prevents hypertension in the Dahl-salt-sensitive (S) rat. The present study was undertaken to determine if pioglitazone modulates pressor responsiveness to vasoactive agents, both in vivo and in vitro. In vivo, pretreatment with pioglitazone inhibited (P < 0.02) pressor responses to both norepinephrine and angiotensin II in conscious Dahl-S, but not in Sprague-Dawley rats. In vitro, pioglitazone augmented the capacity of insulin to inhibit pressor responses of strips of thoracic aortas to norepinephrine, but not to angiotensin. Additionally, in vitro, incubation with insulin plus pioglitazone augmented acetylcholine-induced, but not nitroprusside-induced vasodilation. Pioglitazone pretreatment increased (P < 0.001) in vitro insulin-stimulated glucose uptake in adipose tissue, but not in thoracic aortas of Dahl-S. We hypothesize that pioglitazone attenuates hypertension by modulating the effects of insulin on vascular function, resulting in both blunted vasoconstriction and augmented acetylcholine-induced vasodilation. These alterations are not accounted for by an effect of pioglitazone on glucose uptake by vascular smooth muscle.

Animals↗
PubMed1996

Planning for a community-based hypertension control program in the inner city.

Uncontrolled hypertension is a significant problem among African-Americans residing in inner city environments. To help address the problem, we are developing community-based hypertension control programs in African-American communities located in Milwaukee, Wisconsin and Chicago, Illinois. The Milwaukee program focuses on an entire, diverse inner city area, while the Chicago program is targeted to several more homogeneous African-American neighborhoods. The investigators hypothesize that the success of a hypertension control program will depend on carefully tailoring the educational approaches to the specific characteristics of the target area. Therefore, the study areas that have been selected differ with regard to community size and diversity, community 'stressors' (poverty, unemployment, crime, etc), and types of organizations which are present in the community. This paper describes the background and the rationale for community hypertension control programs in the inner city. The initial approaches to establishing the program by developing interfaces with the community and the gathering of baseline data through household surveys are described.

Community Medicine↗
PubMed1994

Antihypertensive effect of pioglitazone is not invariably associated with increased insulin sensitivity.

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.

Animals↗
PubMed1993

Pioglitazone attenuates hypertension and inhibits growth of renal arteriolar smooth muscle in rats.

Hypertension is frequently associated with insulin resistance. We evaluated the effects of pioglitazone, an agent that increases insulin sensitivity, on the development of hypertension in the Dahl salt-sensitive (Dahl-S) rat and in the one-kidney, one-clip Sprague-Dawley rat. We also evaluated the effects of pioglitazone on growth of cultured preglomerular renal arteriolar smooth muscle cells. In Dahl-S rats fed a 3% NaCl diet, tail systolic blood pressures and direct arterial pressures were lower (P < 0.05) in pioglitazone-treated (20 mg/kg daily by gavage for 3 wk) than in control rats (n = 10 rats/group). In one-kidney, one-clip Sprague-Dawley rats, systolic blood pressures were also lower in pioglitazone-treated animals (P < 0.0001). In vitro, proliferation of arteriolar smooth muscle cells was stimulated (P < 0.01) by insulin, epidermal growth factor (EGF), and fetal calf serum (FCS); pioglitazone (5 microM) reversibly inhibited (P < 0.01) insulin-, EGF-, and FCS-induced proliferation. Pioglitazone (0.01-100 microM) also inhibited insulin- (1 mU/ml), EGF- (100 ng/ml), and 5% FCS-induced [3H]thymidine incorporation in a concentration-dependent manner (P < 0.01). Thus pioglitazone attenuated the development of hypertension in the Dahl-S rat and the one-kidney, one-clip rat. The ability of pioglitazone to inhibit growth of vascular smooth muscle may contribute to its hypotensive effect.

Animals↗
PubMed1993

Sucrose does not raise blood pressure in rats maintained on a low salt intake.

Diets high in sucrose or fructose have been shown by others to induce a modest elevation of blood pressure in rats. The present experiments were conducted to determine whether the sucrose-induced increase of blood pressure is dependent on the intake of sodium chloride. Four groups of Sprague-Dawley rats were studied: 1) a group maintained on a low salt diet and distilled water (0.45% sodium chloride, no added sucrose), 2) a low salt-high sucrose group (0.45% sodium chloride diet and 7% sucrose in distilled water), 3) a high salt group (4% sodium chloride diet and distilled water), and 4) a high salt-high sucrose group on a diet adjusted daily to maintain the same high intakes of sodium chloride and sucrose as those of groups 2 and 3. Systolic blood pressures were measured by tail-cuff plethysmography during weeks 1-3 of treatment, and direct mean arterial blood pressures were recorded in conscious animals during week 4. Animals on the high salt diet gained weight more slowly than those on the low salt intake. On the low sodium chloride intake, blood pressures were not affected by high dietary sucrose (group 1 versus 2). In contrast, on the high sodium chloride intake, blood pressures were 10-14 mm Hg higher in sucrose-drinking animals than in water-drinking animals (group 3 versus 4). The increments in blood pressures of the high sodium chloride-high sucrose group were not accompanied by greater increments in body weight compared with the animals on the high sodium chloride intake alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Gender differences in obesity-related cardiovascular disease risk factors among participants in a weight loss programme.

Obesity is associated with increased cardiovascular disease risk factors in some, but not all, individuals, and blood pressure responses to weight loss are also heterogeneous. The purposes of this study are: (i) to assess associations among cardiovascular disease risk factors in obese individuals and (ii) to determine clinical predictors of a hypotensive response to weight loss. The study was undertaken in 155 consecutive patients enrolled in a weight loss programme. Individuals entering the programme were predominantly women and differences were found between men and women who joined the programme. Before weight loss, obese men exhibited higher cardiovascular disease risk factors (body mass indices, waist-to-hip ratios, systolic and diastolic blood pressures, serum glucose, and lower HDL cholesterol) than did women. However, among women, but not men, cardiovascular disease risk factors clustered in individuals with higher waist-to-hip ratios. Furthermore, in contrast to men, a higher waist-to-hip ratio in women was associated with a reduction in systolic blood pressure in response to weight loss. While it is possible that selection bias may explain gender differences among programme participants, and smaller numbers of men available for study may obscure associations in men, our data document that even at high levels of obesity, waist-to-hip ratios are associated with hypertension and a clustering of cardiovascular disease risk factors in women. We conclude that body fat distribution, as reflected in waist-to-hip ratios, may be a more robust risk factor in female than in male obese patients and that this risk factor extends to those women with high levels of obesity.

Adult↗
PubMed1993

Hypertension: patient evaluation, indications for treatment.

Hypertension in older adults is a prevalent problem with significant morbid consequences, including cerebrovascular, cardiac, and renal disease. Recent studies have established a firm rationale for drug therapy in this population, and therapeutic developments have made effective treatment possible. Patient evaluation includes searches for secondary causes, risk factors for cardiovascular disease, and comorbidity. Antihypertensive therapy requires lifestyle interventions aimed at addressing overall cardiovascular risk factors. Drug therapy decisions are based on level of hypertension, side effects, and comorbid conditions. Older patients can be treated safely and effectively with any of the available antihypertensive agents, but drug selection should be individualized.

Age Factors↗
PubMed1992

Dietary sodium chloride increases blood pressure in obese Zucker rats.

In the rat, elevated arterial pressure is not consistently associated with obesity. The purpose of this study was to compare measurements of blood pressure, cardiac output, and total peripheral resistance in obese and lean Zucker rats on different NaCl intakes. Obese and lean rats drank either water or isotonic NaCl for 18 days. Tail systolic blood pressures of saline-drinking obese rats were higher than all other groups (p less than 0.05). NaCl intake did not affect blood pressure in lean rats, and blood pressures of water-drinking obese rats did not differ from those of lean controls. In a subsequent experiment, direct arterial pressures and cardiac outputs (thermodilution) were measured in separate groups of conscious rats that had been maintained on a 1% or 4% NaCl intake for 12 weeks. Arterial pressure was higher (p less than 0.01) in obese rats fed 4% NaCl (130 +/- 4 mm Hg) than in obese rats fed 1% NaCl (118 +/- 2 mm Hg) or than in lean rats fed either NaCl intake (118 +/- 3 mm Hg and 116 +/- 3 mm Hg, respectively). Cardiac output of obese rats was higher than that of lean rats (p less than 0.01); however, the NaCl-induced increase of blood pressure was accounted for by an increase of peripheral resistance (p less than 0.01). Thus, in contrast to the lean Zucker rat, arterial pressure of the obese Zucker rat is increased by a high dietary intake of NaCl.

Animals↗
PubMed1992

Hemodynamic effects of high dietary intakes of sodium or chloride in the Dahl salt-sensitive rat.

In the Dahl salt-sensitive (Dahl-S) rat, a high sodium without chloride diet (NaAA) and a chloride without sodium diet ("X"Cl) do not increase arterial pressure to the same extent as a high NaCl diet. To explain these differences, hemodynamic responses to acute volume expansion were compared in conscious Dahl-S and Dahl salt-resistant (Dahl-R) rats fed either 7% NaCl, NaAA, or "X"Cl diets for 5 weeks. Before acute volume expansion, on each of the three diets, mean arterial pressures and total peripheral resistances were higher (p less than 0.01) in Dahl-S than in Dahl-R rats, and in Dahl-S, arterial pressure was higher (p less than 0.05 or less) on the 7% NaCl intake than on the other two diets. No group differences were found in cardiac index (thermodilution). Right atrial pressure was also elevated (p less than 0.01) in Dahl-S rats on the 7% NaCl diet. In response to acute volume expansion, arterial pressure did not change, and the decrement of total peripheral resistance was greater in Dahl-S rats than in Dahl-R rats on each of the three diets (p less than 0.05 or less). Assuming that reductions of peripheral resistance in response to acute volume expansion reflect withdrawal of sympathetic tone, these results suggest that sympathetic tone is increased comparably on each of the diets in Dahl-S rats. As suggested by the increased right atrial pressure, higher arterial pressure induced by 7% NaCl may be related to an expanded intravascular volume in conjunction with increased neural activity.

Animals↗