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Objective: To compare a combination of a dihydropyridine calcium-channel blocker with an angiotensin converting enzyme inhibitor vs. monotherapy with one or the other drug and placebo for their effects on home blood pressure (HBP). Methods: After a 2-week placebo wash-out, patients with an elevated office blood pressure (BP) (diastolic 100-109 and systolic

The evaluation of microvascular structure is, in general, not an easy task. Among the methods that may be applied to humans, plethysmographic evaluation of small arteries and wire or pressure micromyography were extensively used in the last decades. The media-to-lumen ratio of small arteries evaluated by micromyography was demonstrated to possess a strong prognostic significance; however, its extensive evaluation is limited by the local invasiveness of the assessment. Noninvasive approaches were then proposed, including capillaroscopy, which provides information about microvascular rarefaction. Recently, the interest of investigators was focused on the retinal microvascular bed. In particular, a noninvasive measurement of the wall-to-lumen ratio of retinal arterioles using scanning laser Doppler flowmetry has been introduced.Recent data suggest a rather good agreement between this approach and micromyographic measurements, generally considered the gold standard approach. Therefore, the evaluation of microvascular structure is progressively moving from bench to bedside, and it could represent, in the immediate future, an evaluation to be performed in all hypertensive patients, in order to obtain a better stratification of cardiovascular risk.

OBJECTIVE To investigate whether the impaired reflex response to cardiopulmonary baroreceptor unloading in hypertensive patients with left ventricular hypertrophy can be promptly improved by a pharmacological challenge. For this purpose we studied the effects of acute digitalis administration on cardiopulmonary baroreflex, evaluated by forearm noradrenaline spillover. METHODS Eleven hypertensives with left ventricular hypertrophy and 10 age- and sex-matched normotensives underwent the application of -5 and -10 mmHg lower-body negative pressure (LBNP) before and after the administration of digitalis. Forearm noradrenaline spillover, measured using a tracer technique, was used to estimate the reflex sympathetic response. RESULTS Under control conditions LBNP evoked a similar fall in right atrial pressure in the two study groups. In the normotensives there was a significant increase in forearm noradrenaline spillover. In the hypertensives no significant changes in forearm noradrenaline spillover were found. Intravenous administration of 0.02 mg/kg lanatoside C was associated with an increase in systolic blood pressure and a reduction in forearm noradrenaline spillover in both groups. In the normotensives the percentage change in forearm noradrenaline spillover induced by LBNP increased significantly in response to digitalis administration. However, digitalis restored the response of forearm noradrenaline spillover to LBNP in the hypertensives, so that no significant difference in this response was detected between the two study groups. Digitalis did not modify the effects of LBNP on cardiac pressures in either group. CONCLUSIONS The present results demonstrate that administration of lanatoside C restores the response of forearm noradrenaline spillover to cardiopulmonary baroreceptor unloading in hypertensive patients with left ventricular hypertrophy. This indicates that the impairment of cardiopulmonary baroreflexes in these patients can be reversed by acute pharmacological treatment. Therefore, impairment of this reflex response seems to be related to functional rather than to structural abnormalities of the hypertrophied ventricle.

Objective: Although the heart is one of the target organs of insulin, it is still unknown whether the effect of insulin on cardiac muscle is preserved in essential hypertension, where insulin resistance has been observed in skeletal muscle. Methods: We evaluated cardiac glucose uptake and the early steps of insulin signalling in spontaneously hypertensive (SHR, 10-12 weeks old) and in age-matched normotensive Wistar-Kyoto (WKY) rats. Cardiac glucose uptake (micromol/100 g per min) was assessed by 2-[14C]deoxyglucose method. After an overnight fast, 16 WKY rats and 17 SHR underwent a hyperinsulinemic euglycemic clamp. In particular, 2-h intravenous (i.v.) infusion of insulin (10 mU/kg per min) or saline (NaCl 0.9%) was administered, followed by an i.v. bolus injection of 2-[14C]deoxyglucose (100 microCi/kg) to measure cardiac glucose uptake. Results: During saline infusion, cardiac glucose uptake was significantly higher in SHR compared to WKY rats (85 +/- 18 versus 8 +/- 3 mg/kg per min, P < 0.01). Furthermore, insulin was able to markedly increase cardiac glucose uptake in WKY rats whereas this insulin action was entirely abolished in SHR; thus, the cardiac glucose uptake became similar in the two rat strains (76 +/- 16 versus 82 +/- 16 mg/kg per min, not significant). More importantly, during saline infusion SHR showed a significantly higher phosphorylation of insulin receptor substance-1 (IRS-1) coupled to enhanced association of the p85 subunit of phosphatidylinositol 3-kinase (PI 3-kinase) to IRS-1 and to an increased PI 3-kinase activity compared to WKY rats. As expected, insulin exposure evoked an activation of its signalling cascade in WKY rats. In contrast, in SHR, the hormone failed to activate post-receptor molecular events. Conclusions: Our data indicate that the heart of SHR shows an overactivity of the proximal steps of insulin signalling which cannot be further increased by the exposure to the hormone. This abnormality may account for the marked increase of basal cardiac glucose uptake and the loss of insulin-stimulated glucose uptake observed in SHR.