Different patterns of H2S/NO activity and cross-talk in the control of the coronary vascular bed under normotensive or hypertensive conditions.

Hydrogen sulfide (H2S) and nitric oxide (NO) play pivotal roles in the cardiovascular system. Conflicting results have been reported about their cross-talk. This study investigated their interplays in coronary bed of normotensive (NTRs) and spontaneously hypertensive rats (SHRs). The effects of H2S- (NaHS) and NO-donors (sodium nitroprusside, SNP) on coronary flow (CF) were measured in Langendorff-perfused hearts of NTRs and SHRs, in the absence or in the presence of propargylglycine (PAG, inhibitor of H2S biosynthesis), L-NAME (inhibitor of NO biosynthesis), ODQ (inhibitor of guanylate cyclase), L-Cysteine (substrate for H2S biosynthesis) or L-Arginine (substrate for NO biosynthesis). In NTRs, NaHS and SNP increased CF; their effects were particularly evident in Angiotensin II (AngII)-contracted coronary arteries. The dilatory effects of NaHS were abolished by L-NAME and ODQ; conversely, PAG abolished the effects of SNP. In SHRs, high levels of myocardial ROS production were observed. NaHS and SNP did not reduce the oxidative stress, but produced clear increases of the basal CF. In contrast, in AngII-contracted coronary arteries of SHRs, significant hyporeactivity to NaHS and SNP was observed. In SHRs, the vasodilatory effects of NaHS were only modestly affected by L-NAME and ODQ; PAG poorly influenced the effects of SNP. Then, in NTRs, the vascular actions of H2S required NO and vice versa. By contrast, in SHRs, the H2S-induced actions scarcely depend on NO release; as well, the NO effects are largely H2S-independent. These results represent the first step for understanding pathophysiological mechanisms of NO/H2S interplays under both normotensive and hypertensive conditions.

Effect of acute and chronic vitamin D administration on systemic renin angiotensin system in essential hypertensives and controls.

AIM: To investigate the systemic renin-angiotensin system (RAS) in essential hypertensives (EH) and controls (C) after short- and long-term vitamin D receptor activation. DESIGN: Ten consecutive EH (under controlled low-salt diet) and 10 C underwent calcitriol administration (0.25 µg bid) for 1 week (Group A). Eighteen consecutive EH under angiotensin II receptor antagonist therapy received a single oral dose of 300,000 IU of cholecalciferol and were followed up for 8 weeks (Group B). METHODS: In basal conditions and at the end of the study (1 week in Group A and 8 weeks in Group B), plasma renin activity (PRA), plasma active renin, aldosterone, and angiotensin II were evaluated, as well as blood pressure, plasma 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D], and PTH. RESULTS: In Group A, plasma 25(OH)D levels in EH and C were below the normal range, although lower levels were found in the former. No association between basal plasma 25(OH)D or 1,25(OH)2D levels and blood pressure values or RAS components was observed either in the whole group or in the two subgroups. Calcitriol administration did not affect any RAS parameter either in EH or in C. In Group B, cholecalciferol significantly increased 25(OH)D and 1,25(OH)2D levels without interfering with the angiotensin II receptor antagonist-induced increase in RAS components. No correlation was found between plasma 25(OH)D or 1,25(OH)2D levels and blood pressure values or RAS parameters before and after cholecalciferol administration. CONCLUSIONS: The present data suggest that, in our experimental conditions, vitamin D receptor activation is unable to influence systemic RAS activity.

High serum levels of CXC (CXCL10) and CC (CCL2) chemokines in untreated essential hypertension.

Hypertension has been suggested to exert pro-inflammatory actions through increased expression of several mediators, including chemokines. Chemokines are involved in inflammatory and autoimmune disorders, and in the formation of atherosclerotic lesions through promotion of inflammatory cell migration. The aim of this study is to evaluate the influence of high blood pressure on circulating levels of the prototype chemokines C-X-C motif ligand (CXCL)10 and C-C motif ligand (CCL)2 in 140 patients with essential hypertension not affected by thyroid disorders or overt autoimmune or inflammatory diseases, and 140 gender- and age-matched healthy controls. Mean CXCL10 and CCL2 levels were significantly higher in hypertensive patients than in controls. Among hypertensive patients, chemokines levels were higher in those with systo-diastolic hypertension compared to those with isolated systolic hypertension. In a multiple linear regression model using CXCL10 or CCL2 as dependent variables and age, body mass index, glycemia, serum creatinine, high-density-lipoprotein (HDL) and low-density-lipoprotein (LDL) cholesterol, triglycerides, and systolic or diastolic blood pressure values as covariates, only systolic or diastolic blood pressure values were significantly related to CXCL10 or CCL2 levels. In conclusion, this study demonstrates increased circulating levels of the prototype chemokines CXCL10 and CCL2 in patients with hypertension.

[Prevention of patient's falls in University Hospital to Sassari, Italy]. / La prevenzione delle cadute in ospedale: progetto dell'Azienda Ospedaliero-Universitaria di Sassari.

The University Hospital has addressed the issue of prevention of falls in hospital with some goals: empowerment of practitioners, patients and their families, development of a tool for classification of the patient to the risk of falls, development of an instrument of signal detection and analysis ofthe fall. Were defined: (a) a scale for assessing risk falls, to be completed upon acceptance by the nurse, made up of several indicators with a score corresponding to each of them, can help to define the patient: low risk, medium risk and high risk, (b) a statement of measures to be implemented depending on the severity of the risk falls, (c) a reportingformfor all fall divided into two sections: nursing and medical (d) a brochure to be delivered at the time acceptance in the department that contains behavioral suggestions for patients and families/caregivers, useful for the prevention of falls. Experimentation of the project took place during the months of October-December 2009 in three UU.00. (Clinic Pulmonology, Neurology and Medical Clinic) with a broad membership of the personnel involved (directors, nursing coordinators, Doctors, Nurses). The results of the trial (of 287 total admissions in the three UO involved, with 90% of evaluation forms filled out, reports offalls were 19 (8%), 17 without loss (85%) and 2 with injury (15%), analyzed for both single UO, which together, have allowed the Department to evaluate the project and to act positively in April 2010 approval of the developed tools and their dissemination to all UO inpatient Company. Were analyzed all report forms received from May 2010 to December 2011. The total admissions in University Hospital, for the whole period examined, were 25,847. The U.O. occurred where the falls are 11 reported (in which the total admissions were 13,791). The reports of falls were 55 (0.40%), of which 29 (53%) from the upright position, 18 (33%) falls out of bed, of which 4 (8%) had fallen from the wheelchair seat and # 4 (8%) falls undetectable; 26 without damage (48%) and 29 with damage (53%).

[Observational study of adverse events in admissions in general hospital of Sassari about corporate planning of clinical risk management]. / Studio osservazionale degli eventi avversi relativi ai ricoveri del 2005, nell'ambito di un programma di gestione del rischio clinico della ASL di Sassari.

In the corporate planning of clinical risk management, we performed an observational retrospective study based on random sampling of admission in General Hospital of Sassari, in 2005. We examined 400 patient clinical documentations in order to find the most frequent adverse events (AE), according to the international literature. We looked for 9 different adverse events; for each of these we elaborated a form personal data and detailed information for each event. During the analysis of the clinical documentations we have found also adverse events not previously classified: they were recorded and classified. We classified the events as explicit, if declared in clinical documentation, and implicit if not declared but clearly present in the records. 47 EA included in the initial 9 categories were found; while other 26 were not included the defined categories, global frequency of AE in our sample resulted: 18.3%. The study is an initial approach to the survey of AE and needs to be refined by determination of liability, severity, predictability, preventability.

[Perceived quality assessment in the University Hospital Authority in Sassary, Italy]. / Valutazione della qualità percepita nell'azienda Ospedaliero Universitaria di Sassari.

In line with the health legislation that introduced a system to monitor and review the quality, the Hospital Authority of University of Sassari has placed among its main objectives the satisfaction of patients/clients and has made an initial assessment of customer satisfaction for users hospitalized in their facilities with the methodology of the questionnaire. It was drawn up a questionnaire to closed questions, with default value scales, divided into 4 areas: 1) Hospitality, 2) Hotel treatment, 3) Professionalism of staff-information related pathology, informed consent, 4) personal opinion of the patient upon discharge. The questionnaire was administered the day of discharge, to users hospitalized of six UO of Hospital Authority in the months of September and October 2009, and patients discharged within 2 months were given a total of 514, of them have completed the testing 290 (54% of discharged patients). The questionnaires were analyzed in the results of both the individual UO involved in both the overall result, persons responsible for each facility was sent a report with the results of its own. The survey results are satisfactory with regard to both positive aspects, that is the overall grade average of 86.23% which to criticism, to which they are planning initiatives for their solution.

Hyperuricemia and Risk of Cardiovascular Outcomes: The Experience of the URRAH (Uric Acid Right for Heart Health) Project.

The latest European Guidelines of Arterial Hypertension have officially introduced uric acid evaluation among the cardiovascular risk factors that should be evaluated in order to stratify patient's risk. In fact, it has been extensively evaluated and demonstrated to be an independent predictor not only of all-cause and cardiovascular mortality, but also of myocardial infraction, stroke and heart failure. Despite the large number of studies on this topic, an important open question that still need to be answered is the identification of a cardiovascular uric acid cut-off value. The actual hyperuricemia cut-off (> 6 mg/dL in women and 7 mg/dL in men) is principally based on the saturation point of uric acid but previous evidence suggests that the negative impact of cardiovascular system could occur also at lower levels. In this context, the Working Group on uric acid and CV risk of the Italian Society of Hypertension has designed the Uric acid Right for heArt Health project. The primary objective of this project is to define the level of uricemia above which the independent risk of CV disease may increase in a significantly manner. In this review we will summarize the first results obtained and describe the further planned analysis.

Reclamation and agricultural reuse of wastewater: the experience of the Cagliari sewage treatment plant (Sardinia, Italy).

In Sardinia, as in many other Mediterranean regions, recurrent droughts and climate change have dramatically reduced available water resources. As a result of this critical situation, in 1995 the Italian Government declared a state of emergency and drew up a program for financial support by the State and local authorities with the aim of reducing this serious deficit. One of the actions focused on reclaiming and reusing the effluent from the sewage treatment plant of Cagliari. This article reports on the multidisciplinary preliminary study performed by the Ente Acque della Sardegna (ENAS) to evaluate the suitability of reusing Is Arenas effluent for irrigation and on the operation of the tertiary treatment plant.

[Quality of the clinical reports: observational study in Sassari]. / La qualità delle cartelle cliniche: studio osservazionale nella ASL di Sassari.

Within the program of clinical risk management, and in particular in the phase of the "knowledge" of company reality, the work deals with the topic of the case history in Sassari' local health authority. A study is treated where, on a sample of about 400 cases history, four definite aspects are considered, in particular those that are regarded as the most important in the risk management and about medical responsability: 1) formal consent; 2) daily clinical allowance; 3) therapeutic card; 4) operating card. The results we got show the presence of a formal consent filled in correctly in 36 cases (9%), completed a daily allowance in 36 cases (9%), therapeutic card in 14 (3.5%) cases, operation card in 21 cases (19% su 116 surgical cases). These data, that have permitted to estimate the specific company reality as from pointed out critical states, show the necessity of working, with involvement of professional doctors, to build a history case model with clear and shared rules where you can clearly find the clinical path of a patient, where everything made is quoted and easily readable when necessary.

Clinical and methodological aspects of endothelial function in patients with systemic autoimmune diseases.

The endothelium is not merely a barrier but it plays a key role in the maintenance of vascular homeostasis. An alteration of the endothelial function (EF) is an early marker of atherosclerosis, also contributing to the development of atherosclerotic lesions and later clinical complications. Systemic autoimmune diseases are characterized by the occurrence of premature atherosclerosis and cardiovascular disease. In view of the prognostic significance of EF for the development of atherosclerotic disease, many studies have evaluated the endothelium in systemic autoimmune diseases, using different techniques. The aim of the present paper is to review the different available techniques to study EF, their advantages and limitations and the data available on the study of EF in systemic autoimmune diseases. Vascular reactivity tests represent the most widely used methods in the clinical assessment of endothelial function. Several techniques were developed to study microcirculation (resistance arteries and arterioles) and macrocirculation (conduit arteries). Studies assessing microvasculature in systemic autoimmune diseases have shown the presence of reduced endothelium dependent vasodilation, while no agreement exists on the presence of endothelium independent alterations. Flow mediated dilation (FMD) has been widely used to evaluate endothelium-dependent vasodilation in peripheral macrocirculation. The majority of studies in systemic autoimmune diseases have shown a decreased brachial artery FMD, whereas endothelium-independent response appears unaffected by the disease in this district. These data strongly underline the different information that could be obtained by different techniques and suggests their combined use in prospective cohorts. Circulating markers of EF include direct products of endothelial cells that change when the endothelium is activated, such as measures of NO biology, inflammatory cytokines, adhesion molecules, as well as markers of endothelial damage and repair. Many of these circulating markers are difficult to measure and quite expensive, and currently are only used in research settings. In view of the complexities in the evaluation of EF, results represent the interaction of several endothelial pathways. No single test currently available is specific for the vascular district tested or the risk factor/diseases considered, and a panel of several tests is therefore needed to characterize the multiple aspects of endothelial biology.

[Chronic inflammation and endothelial dysfunction: analysis of a cohort of patients with SLE and UCTD]. / Flogosi cronica e disfunzione endoteliale: analisi di una coorte di pazienti affetti da LES e UCTD.

OBJECTIVE: Cardiovascular complications, mainly caused by an accelerated atherosclerosis, are one of the leading causes of death and disability in patients with systemic autoimmune diseases. Endothelial dysfunction is considered the earliest and reversible step of atherogenesis. Aim of the present study is to investigate endothelial function (EF) in patients with systemic lupus erythematosus (SLE), undifferentiated connective tissue diseases (UCTD) and correlate the results with clinical and laboratory variables. METHODS: EF was assessed on the peripheral microcirculation by the perfused forearm technique that can estimate both endothelium- dependent and endothelium- independent vasodilatation. The same evaluation has been repeated in two patients after the administration of 20 mg of 6-metilprednisolone. RESULTS: Twenty-three female patients with SLE or UCTD, with a follow up of at least 1 year have been studied and compared with 8 healthy controls matched for epidemiological variables and traditional risk factors for cardiovascular disease. A significant reduction both in endothelium dependent than endothelium independent vasodilatation was observed in both patients groups compared with controls. In addition, UCTD patients demonstrated a significant reduction in the nitric oxide pathway compared with controls and SLE patients. Finally, steroid administration induced an improvement of vascular reactivity. CONCLUSIONS: Despite the well documented side effects of chronic corticosteroid therapy, our data might suggest a role for antinflammatory and immunosuppressive therapy in the prevention of premature atherosclerosis in patients with systemic autoimmune diseases.

Vasoconstriction to endogenous endothelin-1 is increased in the peripheral circulation of patients with essential hypertension.

BACKGROUND: In humans, endothelin (ET)-1 could be implicated in the pathophysiology of several cardiovascular diseases, including essential hypertension. We therefore evaluated the role of ET-1 in control of vascular tone in essential hypertension. METHODS AND RESULTS: We used strain-gauge venous plethysmography to test changes in forearm blood flow induced by intrabrachial infusion of TAK-044 (10, 30, and 100 microgram. 100 mL(-1). min(-1)), an ET(A)/ET(B) receptor antagonist, or sodium nitroprusside (1 and 2 microgram. 100 mL(-1). min(-1)), a vasodilator that acts on smooth muscle cells, in hypertensive patients and healthy controls (n=10 in each group). The NO pathway was also evaluated by infusion of N(G)-monomethyl-L-arginine, (L-NMMA; 10, 30, and 100 microgram. 100 mL(-1). min(-1)), an NO synthase inhibitor, and norepinephrine (3, 9, and 30 ng. 100 mL(-1). min(-1)) as control. Immunoreactive plasma ET-1 was measured by radioimmunoassay. In hypertensive patients, TAK-044 caused a vasodilation that was significantly (P<0.01) increased compared with normotensive subjects. Moreover, vasoconstriction to L-NMMA was significantly (P<0.01) decreased in hypertensive patients compared with controls. In contrast, the vascular responses to sodium nitroprusside and norepinephrine, as well as levels of immunoreactive plasma ET-1, were similar in hypertensive patients and controls. In the study population, vasodilation to TAK-044 and vasoconstriction to L-NMMA showed an inverse correlation (r=-0.56, P<0.05). CONCLUSIONS: These results indicate that TAK-044 caused a greater degree of vasodilation in the forearm vessels of essential hypertensive patients compared with normotensive subjects, an alteration associated with decreased tonic NO release.

Vasodilation to bradykinin is mediated by an ouabain-sensitive pathway as a compensatory mechanism for impaired nitric oxide availability in essential hypertensive patients.

BACKGROUND: In essential hypertension, endothelium-dependent vasodilation is impaired because of reduced nitric oxide (NO) availability, which is mainly caused by oxidative stress. The present study was designed to identify the mechanism(s) responsible for NO-independent vasodilation to bradykinin in patients with essential hypertension. METHODS AND RESULTS: In 16 healthy subjects (49.5+/-5.8 years; 118.6+/-3.5/78.9+/-2.9 mm Hg) and 16 patients with essential hypertension (47.9+/-4.8 years; 154.6+/-4.5/102.9+/-3.2 mm Hg), we measured modifications in forearm blood flow (strain-gauge plethysmography) during intrabrachial infusion of bradykinin (5, 15, or 50 ng/100 mL of forearm tissue per minute) in the presence of saline, N(omega)-monomethyl-L-arginine (L-NMMA; used to inhibit NO synthase; 100 microg/100 mL of forearm tissue per minute), and ouabain (to block Na(+)K(+)/ATPase and prevent hyperpolarization; 0.7 microg/100 mL of forearm tissue per minute). In healthy subjects, vasodilatation to bradykinin was significantly blunted by L-NMMA and unaffected by ouabain. In hypertensive patients, vasodilatation to bradykinin was not modified by L-NMMA, but it was significantly reduced by ouabain. In an adjunctive group of 8 hypertensive patients (49.9+/-3.8 years; 155.9+/-5.5/103.7+/-3.9 mm Hg), the response to bradykinin was repeated during the administration of intrabrachial vitamin C (a scavenger for oxygen free radicals; 8 mg/100 mL of forearm tissue per minute). In these patients, L-NMMA-induced inhibition of vasodilation to bradykinin was restored, and ouabain was no longer effective. In a final group of 6 normotensive controls (45.9+/-4.1 years; 115.1+/-2.9/79.3+/-2.1 mm Hg), vasodilation to bradykinin residual to L-NMMA blockade was further inhibited by simultaneous ouabain infusion. CONCLUSIONS: Vasodilation to bradykinin is impaired in essential hypertensive patients because of an NO-system alteration caused by oxidative stress, and it is mediated by an alternative pathway, possibly involving endothelium-dependent hyperpolarization.

Physical activity prevents age-related impairment in nitric oxide availability in elderly athletes.

BACKGROUND: Aging is associated with increased cardiovascular risk and endothelial dysfunction. Since exercise can improve endothelium-dependent vasodilation, in the present study we tested whether long-term physical activity could prevent aging-related endothelial dysfunction. METHODS AND RESULTS: In 12 young and elderly (age 26.9+/-2.3 and 62.9+/-5.8 years, respectively) healthy sedentary subjects and 11 young and 14 elderly matched athletes (age 27.5+/-1.9 and 66.4+/-6.1 years, respectively), we studied (with strain-gauge plethysmography) forearm blood flow modifications induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 microg/100 mL per minute), an endothelium-dependent vasodilator, at baseline, during infusion of N(G)-monomethyl-L-arginine (L-NMMA) (100 microg/100 mL forearm tissue per minute), a nitric oxide-synthase inhibitor, vitamin C (8 mg/100 mL forearm tissue per minute), an antioxidant, and finally under simultaneous infusion of L-NMMA and vitamin C. The response to sodium nitroprusside (1, 2, and 4 microg/100 mL forearm tissue per minute) was also evaluated. In young athletes and sedentary subgroups, vasodilation to acetylcholine was inhibited by L-NMMA and was not changed by vitamin C. In elderly subjects, vasodilation to acetylcholine was blunted as compared with young subjects in both control subjects and athletes, whereas the response to sodium nitroprusside was similar. Moreover, in elderly athletes, vitamin C did not change the vasodilation to acetylcholine. In contrast, in elderly sedentary subjects, the response to acetylcholine was resistant to L-NMMA. In this subgroup, vitamin C increased the vasodilation to acetylcholine and restored the inhibiting effect of L-NMMA. CONCLUSIONS: These results suggest that regular physical activity can at least in part prevent the age-induced endothelial dysfunction, probably the restoration of nitric oxide availability consequent to prevention of production of oxidative stress.

Mechanisms responsible for endothelial dysfunction associated with acute estrogen deprivation in normotensive women.

BACKGROUND: The goal of this study was to evaluate whether endothelial dysfunction associated with acute estrogen deprivation is caused by an alteration in the L-arginine-nitric oxide (NO) pathway and oxidative stress. Methods and Results-In 26 healthy women (age, 45.7+/-5.4 years) and 18 fertile women with leiomyoma (age, 44.5+/-5.1 years), we studied forearm blood flow (strain-gauge plethysmography) changes induced by intrabrachial acetylcholine (0. 15, 0.45, 1.5, 4.5, or 15 microgram. 100 mL(-1). min(-1)) or sodium nitroprusside (1, 2, or 4 microgram. 100 mL(-1). min(-1)), an endothelium-dependent or -independent vasodilator, respectively. The NO pathway was evaluated by repeating acetylcholine during L-arginine (200 microgram. 100 mL(-1). min(-1); 13 control subjects and 9 patients) or N(G)-monomethyl-L-arginine (L-NMMA; 100 microgram. 100 mL(-1). min(-1); 13 control subjects and 9 patients); production of cyclooxygenase-derived vasoconstrictors was assessed by repeating acetylcholine during indomethacin (50 microgram. 100 mL(-1). min(-1); 13 control subjects and 9 patients) or vitamin C (8 mg. 100 mL(-1). min(-1); 13 control subjects and 9 patients). Patients repeated the study within 1 month after ovariectomy and again after 3 months of estrogen replacement therapy (ERT; 17 beta-estradiol TTS, 50 microgram/d). Basally, vasodilation to acetylcholine was potentiated and inhibited by L-arginine and L-NMMA, respectively (P<0.05), but was unaffected by indomethacin or vitamin C. After ovariectomy, the modulating effect of L-arginine and L-NMMA disappeared, whereas indomethacin and vitamin C potentiated the response to acetylcholine (P<0.05). ERT restored L-arginine and L-NMMA effects on vasodilation to acetylcholine but prevented the potentiation caused by indomethacin or vitamin C. Response to sodium nitroprusside was unaffected by either ovariectomy or ERT. CONCLUSIONS: Endothelial dysfunction secondary to acute endogenous estrogen deprivation is caused by reduced NO availability. Cyclooxygenase-dependent production of oxidative stress could be responsible for this alteration.

Mechanisms responsible for endothelial dysfunction induced by fasting hyperhomocystinemia in normotensive subjects and patients with essential hypertension.

OBJECTIVES: We sought to evaluate whether fasting hyperhomocystinemia reduces endothelial function by oxidative stress in normotensive subjects and hypertensive patients. BACKGROUND: Subjects with hyperhomocystinemia have endothelial dysfunction. METHODS: In 23 normotensive subjects and 28 hypertensive patients, classified into normohomocystinemic and hyperhomocystinemic groups according to homocysteine plasma levels (< 8.7 and >14.6 micromol/l, respectively), we studied forearm blood flow changes (strain-gauge plethysmography) induced by intrabrachial administration of acetylcholine (0.15 to 15 microg/100 ml tissue per min) or sodium nitroprusside (1 to 4 microg/100 ml per min), an endothelium-dependent and -independent vasodilator, respectively. Acetylcholine was repeated with N(G)-monomethyl-L-arginine (L-NMMA; 100 microg/100 ml per min), vitamin C (8 mg/100 ml per min) and L-NMMA plus vitamin C. RESULTS: Normotensive hyperhomocystinemic patients showed a blunted response to acetylcholine and a lower inhibiting effect of L-NMMA on acetylcholine, as compared with normohomocystinemic patients. Although vitamin C was ineffective in normohomocystinemic subjects, it increased the response to acetylcholine and restored the inhibiting effect of L-NMMA on acetylcholine in hyperhomocystinemic patients. Hypertensive hyperhomocystinemic patients showed a reduced response to acetylcholine, as compared with normohomocystinemic subjects. In both subgroups, L-NMMA failed to blunt the response to acetylcholine. The potentiating effect of vitamin C on acetylcholine was greater in hyperhomocystinemic patients than in normohomocystinemic subjects, although it restored the inhibitory effect of L-NMMA on acetylcholine-induced vasodilation to the same extent in both groups. Hyperhomocystinemia did not change the response to sodium nitroprusside. CONCLUSIONS: In normotensive subjects and hypertensive patients, hyperhomocystinemia impairs endothelium-dependent vasodilation. It could be related to oxidant activity.

Adenosine causes the release of active renin and angiotensin II in the coronary circulation of patients with essential hypertension.

OBJECTIVES: The aim of the study was to evaluate whether adenosine infusion can induce production of active renin and angiotensin II in human coronary circulation. BACKGROUND: Adenosine can activate angiotensin production in the forearm vessels of essential hypertensive patients. METHODS: In six normotensive subjects and 12 essential hypertensive patients adenosine was infused into the left anterior descending coronary artery (1, 10, 100 and 1,000 microg/min x 5 min each) while active renin (radioimmunometric assay) and angiotensin II (radioimmunoassay after high performance liquid chromatography purification) were measured in venous (great cardiac vein) and coronary arterial blood samples. In five out of 12 hypertensive patients adenosine infusion and plasma samples were repeated during intracoronary angiotensin-converting enzyme inhibitor benazeprilat (25 microg/min) administration. Finally, in adjunctive hypertensive patients, the same procedure was applied during intracoronary sodium nitroprusside (n = 4) or acetylcholine (n = 4). RESULTS: In hypertensive patients, but not in control subjects, despite a similar increment in coronary blood flow, a significant (p < 0.05) transient increase of venous active renin (from 10.7 +/- 1.4 [95% confidence interval 9.4 to 11.8] to a maximum of 13.8 +/- 2.1 [12.2 to 15.5] with a consequent drop to 10.9 +/- 1.8 [9.7 to 12.1] pg/ml), and angiotensin II (from 14.6 +/- 2.0 [12.7 to 16.5] to a maximum of 20.4 +/- 2.7 [18.7 to 22.2] with a consequent drop to 16.3 +/- 1.8 [13.9 to 18.7] pg/ml) was observed under adenosine infusion, whereas arterial values did not change. Calculated venous-arterial active renin and angiotensin II release showed a strong correlation (r = 0.78 and r = 0.71, respectively; p < 0.001) with circulating active renin. This adenosine-induced venous angiotensin II increase was significantly blunted by benazeprilat. Finally, both sodium nitroprusside and acetylcholine did not affect arterial and venous values of active renin and angiotensin II. CONCLUSIONS: These data indicate that exogenous adenosine stimulates the release of active renin and angiotensin II in the coronary arteries of essential hypertensive patients, and suggest that this phenomenon is probably due to renin release from tissue stores of renally derived renin.

Is Hyperhomocyst(e)inemia a humoral predictor of coronary heart disease?

Elevated plasma homocyst(e)ine levels have prothrombotic and proatherosclerotic effects. Data from prospective studies indicated that plasma homocyst(e)ine acts as a modest independent predictor of coronary heart disease. At present, no conclusive data are available on the possible interaction between hyperhomocyst(e)inemia and hypertension and the occurrence of cardiovascular events. Recent longitudinal studies in high risk patients indicated that hyperhomocyst(e)inemia is strongly associated with recurrent cardiovascular events. However, this finding is not in line with the few available data from prospective studies, which failed to observe a protective role of homocyst(e)ine-lowering therapy in secondary prevention of cardiovascular events. Future results from ongoing larger trials are expected to provide more definitive answers concerning the need to support the routine use of folic acid in patients with CHD. Since the definitive impact of mild hyperhomocyst(e)inemia on coronary heart disease is still to be established, widespread determination of homocyst(e)ine levels is not needed in a general population at the present time. In contrast, knowledge of homocyst(e)inemia may be important for specific groups of individuals, such as high risk patients, and for those patients in whom traditional risk factors do not appear to account for an increased incidence of cardiovascular events.

Ventricular and vascular stiffening in aging and hypertension.

The assessment of arterial stiffness, a common feature of aging, exacerbated by pathological conditions like hypertension, has become an attractive tool for identifying structural and functional changes of the arteries even in an early stage of the atherosclerotic disease. Arterial stiffness has been recognized as an important physio-pathological determinant for the age-related rise in systolic blood pressure, demonstrating also an independent predictive value for cardiovascular events. In the recent decades, many techniques and indices to evaluate vascular stiffness have been developed and extensive data concerning their prognostic value have been collected. Moreover, it has become clear that vessel and heart must be considered as a unique system, in which combined stiffness of vessel and heart interacts to limit cardiovascular performance. In this review, main methods and indices used to estimate arterial and ventricular stiffness are presented, focusing on their alteration in physiological aging and arterial hypertension. Furthermore, the concept of ventricular-arterial coupling is explained in order to give an insight to the interplay between arterial and ventricular stiffness in aging and hypertension.