Biomedical subjects
Publications and source records attributed to Guido Grassi.
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.
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Explore the source record for details and available documents.
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OBJECTIVE: To determine whether in hypertension and in heart failure the occurrence of ventricular arrhythmias is associated with alterations in sympathetic drive and baroreflex function. DESIGN AND METHODS: We studied 28 untreated essential hypertensives (age, 53.0 +/- 1.1 years, mean +/- standard error of the mean), 15 without and 13 with monofocal premature ventricular contractions (PVCs) in Lown class I, and 30 heart failure patients (age, 53.8 +/- 1.3 years) in New York Health Association class II-III, 17 without and 13 with PVCs also in Lown class I. In each patient we measured, along with echocardiographic variables, the beat-to-beat mean blood pressure (Finapress), heart rate (HR) (EKG), muscle sympathetic nerve traffic (MSNA) (microneurography), venous plasma norepinephrine and renin activity (high-pressure liquid chromatography and radioimmunoassay, respectively). Measurements were performed at rest and during arterial baroreceptor stimulation and deactivation via stepwise intravenous infusion of phenylephrine and nitroprusside, respectively. RESULTS: The mean blood pressure, HR and MSNA were similar in hypertensive patients without and with PVCs. However, compared with non-arrhythmic patients, hypertensives with PVCs displayed a baroreflex-HR and baroreflex-MSNA modulation reduced by 27.7 +/- 4.2 and 17.9 +/- 2.8%, respectively (P < 0.05). Heart failure patients with PVCs showed haemodynamic and echocardiographic variables superimposable to those without PVCs. Compared with these patients, however, they exhibited a significant increase in MSNA values (75.8 +/- 3.0 versus 63.6 +/- 2.8 bs/100 hb, P < 0.05), coupled with a significant impairment in baroreflex-HR and baroreflex-MSNA control (-52.5 +/- 5.4 and -37.5 +/- 3.6%, P < 0.01). CONCLUSIONS: These data provide evidence that in both hypertension and heart failure, sympathetic and baroreflex mechanisms exert a pro-arrhythmogenic role. This role, however, appears to be more pronounced in heart failure than in hypertension, in which the impaired vagal function may exert a concomitant favouring effect.
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BACKGROUND: Previous studies have shown that obesity is characterized by a sympathetic overactivity coupled with an insulin resistance state and a baroreflex impairment. The present study was set out to compare the effects of peripheral versus central obesity on sympathetic, metabolic and reflex function. METHODS: In 36 lean subjects (age 35.8 +/- 1.4 years, mean +/- SEM), 20 subjects with peripheral obesity (PO) and 26 subjects with central obesity (CO), all age-matched and with normal blood pressure values, we measured beat-to-beat arterial blood pressure (Finapres), heart rate (HR, ECG), homeostasis model assessment (HOMA) index, plasma norepinephrine (NE, high-performance liquid chromatography) and postganglionic muscle sympathetic nerve traffic (MSNA, microneurography) at rest and during baroreceptor stimulation and deactivation induced by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. RESULTS: Both HOMA index, NE and MSNA values were significantly increased (P < 0.01) in obese as compared with lean individuals. Subjects with CO displayed MSNA and HOMA values significantly greater than those found in individuals with PO (65.4 +/- 2.0 versus 47.9 +/- 1.9 bs/100hb and 2.85 +/- 0.10 versus 2.43 +/- 0.11 a.u., respectively, P < 0.05 for both). Both in male and female subjects with CO or PO, MSNA, HOMA index and waist-to-hip ratio were significantly related to each other. Baroreceptor-HR and -MSNA control was significantly (P < 0.01) impaired in obese as compared with lean subjects, the degree of impairment being similar in CO and PO. CONCLUSIONS: These data suggest that CO is characterized by a sympathetic activation greater for magnitude than that detectable in PO. This appears not to be related to gender or to baroreflex mechanisms but rather to metabolic factors, i.e. to the greater insulin resistance characterizing CO.
OBJECTIVE: It is well established that adequate blood pressure (BP) control characterizes only a fraction of treated hypertensive patients. Few reports are available on BP control in relation to the cardiovascular risk profile in patients followed by specialist physicians. METHODS: We evaluated the cardiovascular risk profile (according to recent ESH/ESC Guidelines), antihypertensive drug treatment and systolic and diastolic blood pressure values (SBP/DBP) by semi-automatic BP monitoring in 2775 hypertensive patients, aged 60.6 +/- 16.1 years (mean +/- SD), followed by 131 specialist centres in northern (34.5%), central (28.1%) and southern (37.4%) Italy. Of these patients, 94.6% received antihypertensive treatment with one (36.9%) or more (57.7%) drugs. RESULTS: Optimal SBP and DBP control (< 140/90 mmHg) was shown by 37.5% of the patients, the rate of controlled values being much greater for DBP (64.4%) than for SBP (40.2%). About one-third of patients displayed BP values in the higher range (>/= 160/95 mmHg). No difference in BP control was found in relation to different geographic areas, patient's gender, occupational activity and attitude to the use of home blood pressure monitoring. BP control was inversely related to patient's age and directly related to educational level. It was more manifest in low- or medium-risk categories than in higher-risk patients (43.2 versus 34.9%). Follow-up visits performed after 6 and 12 months after patient enrollment have shown an improvement in blood pressure control (from 40.7 to 51.8%), related to therapeutic modifications and better compliance. CONCLUSIONS: These data provide evidence that BP control in different Italian geographic areas remains largely inadequate, particularly for SBP and high-risk patients. They also suggest that an improvement in treatment compliance may produce favourable therapeutic effects.
Most hypertensive patients require more than one medication to effectively control elevated blood pressure (BP) values. This multicenter, randomized, double-blind study was aimed at testing the efficacy and safety of the combination of low-dose nifedipine GITS 20 mg/ losartan 50 mg compared with either monotherapy in patients with grade 1 to 3 hypertension over an eight-week period. Of 352 patients enrolled in the study, 300 were randomized. All the three treatments lowered elevated BP without clinically relevant changes in heart rate. All the three treatments lowered mean 24-hour diastolic BP: nifedipine GITS/losartan -10.6 mm Hg, losartan -5.4 mm Hg, nifedipine GITS 20 mg -8.0 mm Hg. There was a statistically significant difference of diastolic BP change between patients receiving losartan compared with those receiving combination treatment (P < 0.05). Diastolic BP trough-to-peak ratio and smoothness index were highest in the patient group receiving combination therapy (70%). Nifedipine GITS monotherapy had the highest systolic BP trough-to-peak ratio of all treatment arms (78%) and higher diastolic BP trough-to-peak ratio and smoothness index than losartan monotherapy. All treatments were safe. These data provide evidence that in hypertensive patients combination of nifedipine GITS 20 mg and losartan 50 mg improves control of systolic and diastolic BP compared with either monotherapy.
PURPOSE OF REVIEW: This paper will provide an up-to-date overview of the adrenergic effects of the different classes of antihypertensive drugs in uncomplicated hypertension, as well as in hypertension associated with obesity, renal failure, diabetes or congestive heart failure. RECENT FINDINGS: Animal and human studies unequivocally show that sympathetic activation characterizes the hypertensive state and participates in the development, maintenance and progression of elevated blood pressure values. Evidence has also been provided that elevated sympathetic cardiovascular influences are involved in the pathogenesis of left ventricular hypertrophy, vascular hypertrophy and atherogenesis, as well as in the occurrence of metabolic disarray (i.e. metabolic syndrome, hypercholesterolemia, hyperinsulinemia and insulin resistance), which frequently accompany the hypertensive state. Antihypertensive drugs with confirmed sympathoinhibitor effects are represented by beta-blockers, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. In the case of the latter two classes of antihypertensive compounds the sympathoinhibitory effects have been shown to be associated with beneficial metabolic and cardiovascular effects, a finding that supports the use of these drugs in complicated hypertension. SUMMARY: Investigation of the adrenergic effects of antihypertensive drugs has had a significant impact on cardiovascular pharmacology and hypertension treatment. Although remarkable progress has been made on this topic in recent years, future studies aimed at assessing the sympathetic effects of combination drug treatment will be helpful in improving the clinical use of the association of two or more drugs in hypertension treatment.
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The sympathetic nervous system has moved towards center stage in cardiovascular medicine. The importance of the sympathetic activation in heart failure and in renal insufficiency progression and mortality is indeed now well established. In essential hypertension evidence has been provided that this may be the case, because sympathetic overactivity is a key factor in the pathophysiology of the disease, thereby promoting not only the blood pressure increase but also the development and progression of the hypertension-related cardiovascular and metabolic complications, such as left ventricular hypertrophy, vascular hypertrophy, endothelial dysfunction, cardiac rhythm disturbances and insulin resistance. In this review article the main pathophysiologic and mechanistic features of the sympathetic overactivity characterizing the essential hypertensive state will be examined. This will be followed by an analysis of the effects of 1) the hyperadrenergic state on the cardiovascular risk profile as well as on the end organ damage and 2) the different antihypertensive compounds on sympathetic and baroreflex function. The rationale for obtaining during antihypertensive drug treatment an effective sympathoinhibition will be finally highlighted.
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Previous studies have shown that congestive heart failure is characterized by sympathetic and reflex dysfunctions. Whether these alterations are potentiated in the presence of obesity and hypertension, two conditions that also display neuroadrenergic abnormalities and markedly increase the risk of heart failure, is unknown. In 14 healthy control subjects (C; age, 55.1+/-3.0 years; mean+/-SEM), 13 lean hypertensive subjects (H), 15 obese normotensive subjects (O), 14 lean normotensive subjects with congestive heart failure (CHF, New York Heart Association class II), 14 lean hypertensive subjects with CHF (CHFH), 14 obese normotensive subjects with CHF (CHFO), and 13 obese hypertensive subjects with CHF (CHFOH), all age-matched with C, we measured mean blood pressure (Finapres), heart rate (ECG), and muscle sympathetic nerve traffic (MSNA, microneurography) at rest and during baroreflex testing. Compared with C, body mass index was similarly increased in O, CHFO, and CHFOH, whereas mean blood pressure was similarly increased in HF, CHFH, and CHFOH, and left ventricular ejection fraction (echocardiography) was similarly reduced in CHF, CHFH, CHFO and CHFOH. Compared with C, MSNA was significantly increased in O, H, and CHF (43.0+/-2.2 versus 54.1+/-2.8, 53.1+/-2.5, and 57.4+/-2.8 bursts/100 heart beats, P<0.01). When O or H was combined with CHF, the MSNA increase was significantly more pronounced and maximal when O and H were concomitantly associated with CHF. Baroreflex sensitivity was reduced in O and H, with a further reduction in CHF and a minimal value in CHFOH. These data show that the sympathetic activation characterizing CHF is markedly potentiated when O and H alone or combined together are associated with a low cardiac output state and that this may depend on an arterial baroreflex impairment.
BACKGROUND: Human aging is characterized by a marked increase in muscle sympathetic nerve traffic (MSNA). No information exists, however, on the effects of aging on skin sympathetic nerve traffic (SSNA) and on its reflex modulation by thermoregulatory mechanisms. METHODS AND RESULTS: In 13 young, 11 middle-aged, and 12 elderly healthy subjects, we measured arterial blood pressure (Finapres), skin temperature (thermocouples), and resting MSNA and SSNA (microneurography). Measurements also included the SSNA responses to (1) an acute increase and reduction (+/-8 degrees C) in room temperature, each lasting 45 minutes and (2) an acoustic stimulus capable to trigger an emotional arousal. Although resting MSNA was progressively and significantly (P<0.05) increased from young to middle-aged and elderly groups, SSNA was significantly (P<0.05) reduced in the latter compared with the former 2 groups. Cold exposure induced a SSNA increase that was significantly (P<0.01) smaller in the elderly than in young and middle-aged subjects. Conversely, heat exposure induced a SSNA reduction that was significantly (P<0.05) smaller in elderly than in young and middle-aged subjects. Compared with SSNA in young individuals, the SSNA change from cold to warm temperature was reduced by 61% in the elderly group. This was not the case, however, for the SSNA responses to the arousal stimulus, which were superimposable in the 3 groups. CONCLUSIONS: These data provide the first demonstration of a dichotomy in the MSNA and SSNA responses to aging. They also show that aging markedly impairs thermoregulatory control of SSNA and that this impairment might participate at the age-related SSNA decrease.
The compound 3-hydroxypropionaldehyde (3-HPA), together with HPA hydrate and HPA dimer, in aqueous solution forms a system with interesting chemical properties. Therefore, 3-HPA has attracted attention by the chemical industry for use as a precursor in the production of plastics, acrylic acid, and 1,3-propanediol and by the food industry, in using 3-HPA-producing Lactobacillus reuteri as a probiotic. To produce 3-HPA in high yield from glycerol, L. reuteri was used as a biotransformation system. A convenient chromatographic purification method was developed, and purified 3-HPA was analyzed using electrospray ionization mass spectrometry and (13)C NMR. Quantitative (13)C NMR revealed a concentration-dependent distribution of the three compounds forming the HPA system. At concentrations above 1.4 M, the HPA dimer was predominant. However, at concentrations relevant for biological systems, HPA hydrate was the most abundant, followed by the aldehyde form. Our results indicate that the dimeric form with expected antibiotic properties should not be the active form.
Antihypertensive treatment with dihydropyridines may be accompanied by sympathetic activation. Data on whether this is common to all compounds and similar in the various phases of treatment are not univocal, however. In 28 untreated essential hypertensives (age, 56.4+/-1.8 years; mean+/-SEM) finger blood pressure (BP, Finapres), heart rate (HR, ECG), plasma norepinephrine (NE, high-performance liquid chromatography), and muscle sympathetic nerve traffic (MSNA, microneurography) were measured at rest and during baroreceptor manipulation (vasoactive drugs) in the placebo run-in period and after randomization to double-blind acute and chronic (8 weeks) felodipine (10 mg/d, n=14) or lercanidipine (10 mg/d, n=14). Acute administration of both drugs induced pronounced BP reductions and marked increases in HR, NE, and MSNA. After 8 weeks of treatment, BP reductions were similar to those observed after acute administration, whereas HR, NE, and MSNA responses were markedly attenuated (-7%, -32%, and -14%, respectively; P<0.05). There was a small residual increase in sympathetic activity in the felodipine group, whereas in the lercanidipine group, all adrenergic markers returned to baseline values. Baroreflex control of HR and MSNA was markedly impaired (-42% and -48%, respectively) after acute drug administration, with a recovery and complete resetting during chronic treatment. Thus, the sympathoexcitation induced by 2 different dihydropyridines is largely limited to the acute administration. The 2 drugs have, nevertheless, a different chronic sympathetic effect, indicating that dihydropyridines do not homogeneously affect this function. The acute sympathoexcitation, but not the small between-drugs differential chronic adrenergic effect, is accounted for by baroreflex impairment.