IntroductionThe reason why hyperinsulinemia is associated with essential hypertension is not known. To test the hypothesis of a pathophysiologic link mediated by the sympathetic nervous system, we measured the changes in forearm norepinephrine release, by using the forearm perfusion technique in conjunction with the infusion of tritiated NE, in patients with essential hypertension and in normal subjects receiving insulin intravenously (1 mU/ kg per min) while maintaining euglycemia.Hyperinsulinemia (50-60 jsU/ml in the deep forearm vein) evoked a significant increase in forearm NE release in both groups of subjects. However, the response of hypertensives was threefold greater compared to that of normotensives (2.28±45 ng. liter-' * min' in hypertensives and 0.80±0.27 ng. liter-' in normals; P < 0.01). Forearm Although the coexistence ofhyperinsulinemia and essential hypertension has long been recognized (1-3), the nature and the significance of this association are far from being completely elucidated. A critical question is whether hyperinsulinemia is causally related to the development of hypertension and, if so, what mechanism underlies insulin action on blood pressure regulation. The question is under active investigation but the data available so far are not entirely consistent. Substantial evidence favoring a causal role of insulin comes essentially from the studies in fructose-fed rats (4-6). In this model, insulin resistance, hyperinsulinemia, and hypertension develop and this sequence may be interrupted by preventing either insulin resistance with physical exercise or hyperinsulinemia with somatostatin (5, 6).The relationship between insulin and human hypertension has been extensively investigated on epidemiological ground, less so from a mechanistic standpoint. The available clinical data, however, tend to support the concept that the two factors must be linked by pathophysiologic mechanisms. Particularly relevant is the observation that a program of physical activity or body weight control leads to a parallel reduction of hyperinsulinemia and blood pressure levels (7). Of interest is also the recent observation that in the offspring of essential hypertensive parents insulin resistance and hyperinsulinemia are demonstrable before the development of high blood pressure (8).Among the various factors considered as potential links between insulin and blood pressure, the sympathetic nervous system is indicated as a prime candidate for a number of reasons: (a) in hypertensive patients, glucose intolerance and insulin resistance with attendant hyperinsulinemia have been amply demonstrated (3, 9, 10); (b) in normal individuals, insulin evokes sympathetic overactivity (1 1, 12); (c) increased sympathetic activity in essential hypertension, particularly in the mild form of young hypertensives, has been documented by a variety of approaches (13,14); and (d) sympathetic overactivity may be potentially responsible for elevated blood pressure (15) and may antagonize insulin action (16)(17)(18)(19)(20). Ba...

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Background — Although thyroid hormone (TH) exerts relevant effects on the cardiovascular system, it is unknown whether TH also regulates vascular reactivity in humans. Methods and Results — We studied 8 patients with hyperthyroidism, basally (H) and 6 months after euthyroidism was restored by methimazole (EU). Thirteen healthy subjects served as control subjects (C). We measured forearm blood flow (FBF) by strain-gauge plethysmography during intrabrachial graded infusion of acetylcholine, sodium nitroprusside (SNP), norepinephrine, and L-NMMA (inhibitor of NO synthesis). Basal FBF (in mL · dL −1 · min −1 ) was markedly higher in H than in C (5.8±1.2 and 1.9±0.1, respectively; P <0.001) and was close to normal in EU (2.6±0.3, P <0.01 versus H). During acetylcholine infusion, FBF increased much more in H (+33±5) than in C (+14±3, P <0.01 versus H) and in EU (+20±5, P =0.01 versus H and P =NS versus C). In contrast, the response to SNP infusion was comparable in the patients and control subjects. During norepinephrine infusion, the fall in FBF was much more pronounced in H (−6±1) than in C (−0.7±0.3, P <0.005 versus H) and in EU (−1.5±0.3, P <0.01 versus H). Finally, inhibition of NO synthesis by L-NMMA decreased FBF by 2.8±0.6, 0.61±0.7, and 1.4±0.3 in H, C, and EU, respectively (H versus C and EU, P <0.05). Conclusions — In hyperthyroidism, (1) the marked basal vasodilation is largely accounted for by excessive endothelial NO production, (2) vascular reactivity is exaggerated because of enhanced sensitivity of the endothelial component, (3) the vasoconstrictory response to norepinephrine is potentiated, and (4) this abnormal vascular profile is corrected when euthyroidism is restored by medical therapy. The data demonstrate that vascular endothelium is a specific target of TH.

These data demonstrate that early treatment of large MI with GH attenuates the early pathologic LV remodeling and improves LV function.