The main goal of treating hypertension is to reduce blood pressure to physiological levels and thereby prevent risk of cardiovascular disease and hypertension-associated target organ damage. Despite reductions in major risk factors and the availability of a plethora of effective antihypertensive drugs, the control of blood pressure to target values is still poor due to multiple factors including apparent drug resistance and lack of adherence. An explanation for this problem is related to the current reductionist and ‘trial-and-error’ approach in the management of hypertension, as we may oversimplify the complex nature of the disease and not pay enough attention to the heterogeneity of the pathophysiology and clinical presentation of the disorder. Taking into account specific risk factors, genetic phenotype, pharmacokinetic characteristics, and other particular features unique to each patient, would allow a personalized approach to managing the disease. Personalized medicine therefore represents the tailoring of medical approach and treatment to the individual characteristics of each patient and is expected to become the paradigm of future healthcare. The advancement of systems biology research and the rapid development of high-throughput technologies, as well as the characterization of different –omics, have contributed to a shift in modern biological and medical research from traditional hypothesis-driven designs toward data-driven studies and have facilitated the evolution of personalized or precision medicine for chronic diseases such as hypertension.

This comment focuses on the background and implications of a study published in this issue of Clinical Science by Franzoni and colleagues showing that physical training improves nitric oxide availability and microvascular distensibility not only in young, but also in elderly, individuals. The main features of the study as well as its potential limitations will be also highlighted.

Congestive heart failure (CHF) is characterized by a sympathetic activation and a baroreflex impairment whose degree is directly related to the clinical severity of the disease. However, whether these abnormalities vary according to the ischaemic or idiopathic dilated nature of the CHF state has not been conclusively documented. In patients with a clinically stable, chronic CHF state in New York Heart Association functional class II and III, due either to ischaemic heart disease (IHD; n = 22, age 60.3±2.4 years, means±S.E.M.) or to idiopathic dilated cardiomyopathy (IDC; n = 20, age 58.9±2.8 years), and in 30 age-matched controls, we measured arterial blood pressure (using a Finapres device), heart rate (by electrocardiogram) and postganglionic muscle sympathetic nerve traffic (by microneurography) at rest and during baroreceptor manipulation induced by the vasoactive drug-infusion technique. Blood pressure values were not significantly different in CHF patients and controls. Compared with controls, heart rate was similarly increased and left ventricular ejection fraction (by echocardiography) similarly reduced in CHF patients with IHD or IDC. Muscle sympathetic nerve traffic was significantly greater in CHF patients than in controls, and did not differ between patients with IHD or IDC (67.3±4.2 and 67.8±3.8 bursts/100 heart beats respectively). This was also the case for the degree of baroreflex impairment. These data show that CHF states due to IHD or to IDC are characterized by a similar degree of peripheral sympathetic activation and by a similar impairment of the baroreflex function. Thus the neuroadrenergic and reflex abnormalities characterizing CHF are independent of its aetiology.

1. Although plasma noradrenaline and muscle sympathetic nerve traffic have been shown to be suitable markers of sympathetic activity in man, no study has systematically compared the reproducibility and sensitivity of these two indices of adrenergic tone. 2. Reproducibility data were collected in 10 subjects, in whom plasma noradrenaline was assessed by HPLC on blood samples withdrawn from an antecubital vein and efferent postganglionic muscle sympathetic nerve activity was measured by microneurography from a peroneal nerve, together with arterial blood pressure (Finapres technique). Measurements were obtained in a first session (session 1), 60 min later (session 2) and after 14 days (session 3). While muscle sympathetic nerve activity values recorded in the three different experimental sessions were closely and significantly correlated with each other ( r always >0.90, P < 0.001), noradrenaline showed a less significant correlation between sessions 1 and 2 ( r = 0.71, P < 0.05) or no correlation between sessions 1 and 3 ( r = 0.45, P not significant). 3. Sensitivity data were collected by evaluating muscle sympathetic nerve activity and noradrenaline values in three different age groups (young, middle-age and old subjects, n = 18), in three groups with different blood pressures (normotensive, mild and severe hypertensive subjects, n = 30) and in a group of eight subjects before and after a physical training programme, i.e. conditions known to increase or reduce sympathetic cardiovascular drive. Muscle sympathetic nerve activity was significantly increased by aging and hypertension, and reduced by physical training. The noradrenaline changes were much less marked and consistent. 4. These data suggest that muscle sympathetic nerve activity has a greater short- and medium-term reproducibility than noradrenaline. In several conditions known to modify sympathetic cardiovascular drive muscle sympathetic nerve activity also appears to change more clearly than noradrenaline.

1. The effects of selective deactivation and stimulation of cardiopulmonary receptors on plasma noradrenaline (radioenzymatic method) were studied in nine normotensive subjects by reducing and increasing central venous pressure for 20 min via lower body suction and leg-raising manoeuvres that did not alter arterial blood pressure and heart rate. 2. Deactivation of cardiopulmonary receptors was accompanied by a rise in plasma noradrenaline that achieved a peak within 5 min (91.8 ± 22%, mean ± se ) and was then sustained. Stimulation of cardiopulmonary receptors was accompanied by a fall in plasma noradrenaline (−16.6 ± 3.4%) that levelled off at the second minute and was then sustained. 3. On average the increase and the reduction in plasma noradrenaline had a time course and a magnitude similar to the increase (80.5 ± 10.5%) and the reduction (−28.4 ± 5%) in forearm vascular resistance (derived from plethysmographic flow measurement) concomitantly caused by cardiopulmonary receptors. Furthermore, analysis of individual data showed that changes in plasma noradrenaline and forearm vascular resistance were linked by a positive relationship ( r = 0.64). 4. Thus the cardiopulmonary receptor reflex can produce rapid, marked and sustained changes in both plasma noradrenaline and forearm vasomotor tone. This is in sharp contrast with the previously observed inability of the carotid baroreflex to alter both these humoral and haemodynamic variables. Taken together these findings support the hypothesis that sympathetic tone to skeletal muscle is an important determinant of the concentration of plasma noradrenaline in blood.