Complications related to fracture treatment in HIV patients: a case report.

We present the case report of a 40-year-old woman who was HIV-positive in Highly Active Anti-Retroviral Therapy (HAART) and affected by femural pertrochanteric fracture, which was treated by endomedullary nailing. Two years after the surgical operation, the woman developed an aseptic symptomatic osteolysis around the implant. Hardware removal was resolutive. Aseptic and septic hardware mobilization, hardware removal, and implant decision in HIV patients with pertrochanteric fractures is discussed. The authors suggest close follow-up and prompt hardware removal, as soon as X-rays demonstrate healing signs, in HIV patients with fracture fixation, if general condition allows.

Quantitative versus qualitative modeling: a complementary approach in ecosystem study.

Natural disturbance or human perturbation act upon ecosystems by changing some dynamical parameters of one or more species. Foreseeing these modifications is necessary before embarking on an intervention: predictions may help to assess management options and define hypothesis for interventions. Models become valuable tools for studying and making predictions only when they capture types of interactions and their magnitude. Quantitative models are more precise and specific about a system, but require a large effort in model construction. Because of this very often ecological systems remain only partially specified and one possible approach to their description and analysis comes from qualitative modelling. Qualitative models yield predictions as directions of change in species abundance but in complex systems these predictions are often ambiguous, being the result of opposite actions exerted on the same species by way of multiple pathways of interactions. Again, to avoid such ambiguities one needs to know the intensity of all links in the system. One way to make link magnitude explicit in a way that can be used in qualitative analysis is described in this paper and takes advantage of another type of ecosystem representation: ecological flow networks. These flow diagrams contain the structure, the relative position and the connections between the components of a system, and the quantity of matter flowing along every connection. In this paper it is shown how these ecological flow networks can be used to produce a quantitative model similar to the qualitative counterpart. Analyzed through the apparatus of loop analysis this quantitative model yields predictions that are by no means ambiguous, solving in an elegant way the basic problem of qualitative analysis. The approach adopted in this work is still preliminary and we must be careful in its application.

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.

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.

Exclusion of the ACE D/I gene polymorphism as a determinant of endothelial dysfunction.

A deletion/insertion (D/I) polymorphism within the ACE gene may increase the risk of cardiovascular events through still unknown mechanisms. The latter may involve increased angiotensin II-induced NO breakdown and/or reduced agonist-mediated NO release. We therefore investigated whether the D allele of the ACE gene affects endothelium-dependent vasodilatation in mild-to-moderate primary hypertensive patients and healthy normotensive subjects. We compared in a cross-sectional study the forearm blood flow response of the 3 D/I genotypes with 5 incrementally increasing doses of the endothelium-dependent vasodilator acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 microg. 100 mL(-1). min(-1)) in 142 subjects: 103 mild-to-moderate uncomplicated primary hypertensives (49.3+/-9.1 years old, 152+/-11/99+/-5 mm Hg) and 39 normotensives (44.6+/-15.3 years old, 122+/-12/78+/-6 mm Hg). We also assessed the endothelium-independent vasodilatation in the forearm, as blood flow response to 3 incrementally increasing doses of sodium nitroprusside (1, 2, and 4 microg. 100 mL(-1). min(-1)). The overall genotype distribution was II, n=10; ID, n=70; and DD, n=62. It did not differ significantly between primary hypertensives and normotensives. A significant blunting of endothelium-dependent vasodilatation in primary hypertensive patients compared with normotensive subjects (P:<0.001) was found. No effect of the DI genotype on endothelium-dependent and -independent vasodilatation was detected. Thus, these results obtained in a relatively large population do not support the contention that the D allele is associated with a blunting of either stimulated endothelial NO or donated NO responses in both mild-to-moderate primary hypertensive patients and normotensive subjects.

Restoration of nitric oxide availability after calcium antagonist treatment in essential hypertension.

Essential hypertension is associated with impaired endothelium-dependent vasodilation caused by oxygen free radical-induced nitric oxide (NO) breakdown. Because calcium antagonists can improve endothelial function in patients with essential hypertension, in this study we tested the hypothesis that this beneficial effect could be related to restoration of NO availability by antioxidant properties. In 15 healthy subjects and 15 hypertensive patients, we studied forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (ACh; 0.15, 0.45, 1.5, 4.5, and 15 microg/100 mL per minute), an endothelium-dependent vasodilator in basal conditions, during infusion of N:(G)-monomethyl-L-arginine (L-NMMA, 100 microg/100 mL forearm tissue per minute), an NO-synthase inhibitor, vitamin C (8 mg/100 mL forearm tissue per minute), and finally, simultaneous infusion of L-NMMA and vitamin C. The response to sodium nitroprusside (SNP; 1, 2, and 4 microg/100 mL forearm tissue per minute) was also evaluated. In control subjects, vasodilation to ACh was inhibited by L-NMMA and not changed by vitamin C. In hypertensive patients, vasodilation to ACh was blunted as compared with control subjects and resistant to L-NMMA. Vitamin C, which decreased plasma isoprostanes and increased plasma antioxidant capacity, increased the response to ACh and restored the inhibiting effect of L-NMMA. In hypertensive patients, the study was repeated after 3-month treatment with nifedipine gastrointestinal therapeutic system (30 to 60 mg/daily). Nifedipine treatment decreased circulating plasma lipoperoxides and isoprostanes and increased plasma antioxidant capacity. Moreover, nifedipine increased the vasodilation to ACh but not to SNP and restored the inhibiting effect of L-NMMA on ACh-induced vasodilation, whereas vitamin C no longer exerted its facilitating activity. These results indicate that nifedipine increases endothelium-dependent vasodilation by restoring NO availability, an effect probably determined by antioxidant activity.

Relationship between the circulating and vascular renin-angiotensin system and the vasodilating effect of captopril in human hypertension.

A vascular renin-angiotensin system (RAS) is present in the forearm vasculature of essential hypertensive patients and is closely related to the circulating renin profile. To test whether the haemodynamic effect of acute intrabrachial administration of captopril is related to the circulating and/or vascular RAS, 31 hypertensive patients were selected and divided into four groups according to their different circulating RAS profile (n = 7 hypertensive patients with primary aldosteronism and suppressed plasma renin activity; n = 7 low renin essential hypertensive patients; n = 8 normal renin essential hypertensive patients; n = 9 high renin renovascular hypertensive patients). The forearm net balance of active renin, plasma renin activity and angiotensin II, obtained by intrabrachial infusion of the beta-adrenergic receptor agonist isoproterenol (0.03, 0.1, 0.3 microg/100 ml/min) and calculated as the product of the venous-arterial plasma concentration gradient and forearm blood flow (FBF), was closely related to the circulating RAS. Captopril (0.25, 2.5, 25 microg/100 ml/min per 20 min each dose) unchanged basal FBF in the primary aldosteronism and low renin groups (FBF increase: from 3.9 +/- 0.4 to a maximum of 4.1 +/- 0.5 and from 3.8 +/- 0.3 to a maximum of 4.3 +/- 0.5 ml/100 ml/min, respectively), whereas it caused slight vasodilation in the normal renin group (from 3.9 +/- 0.3 to a maximum of 5.3 +/- 0.7 ml/100 ml/min), and pronounced vasodilation in the high renin group (from 4.0 +/- 0.4 to a maximum of 6.4 +/- 0.5 ml/100 ml/min). Captopril-induced vasodilation showed a significant direct correlation with the circulating and vascular RAS. The present data, while confirming the existence of a vascular RAS in the forearm of hypertensive patients indicate that the acute vasodilating effect of intrabrachial captopril is linked to a stimulated RAS, either circulating or vascular, supporting the evidence that, in acute conditions, ACE inhibitors exert their vasodilating effect through the RAS blockade.

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.

Angiotensin II and sympathetic activity in sodium-restricted essential hypertension.

Angiotensin II (Ang II) potentiates sympathetic neurotransmission by presynaptic facilitation of norepinephrine release. We investigated whether endogenous Ang II modulates peripheral sympathetic activity in sodium-depleted essential hypertensive patients. We evaluated the effect of intrabrachial infusion of saralasin, an Ang II antagonist (5 micrograms/100 mL forearm tissue per minute), and benazeprilat, an angiotensin-converting enzyme inhibitor (2 micrograms/100 mL forearm tissue per minute), on forearm vasoconstriction (measured by strain-gauge venous plethysmography) induced by the application of lower body negative pressure (-10 mm Hg for 5 minutes). Both saralasin and benazeprilat (n = 6 for each group) blunted the vasoconstrictor action of lower body negative pressure, suggesting that circulating Ang II modulates peripheral sympathetic activity. In addition, since beta-adrenoceptor stimulation can activate the production of vascular Ang II, the effect of saralasin and benazeprilat on lower body negative pressure application was evaluated in the presence of isoproterenol (0.09 microgram/100 mL forearm tissue per minute) and propranolol (10 micrograms/100 mL forearm tissue per minute). In two other groups of hypertensive patients, isoproterenol infusion increased the release of Ang II in the forearm vasculature (arteriovenous values measured by radioimmunoassay). Furthermore, isoproterenol potentiated lower body negative pressure-induced vasoconstriction. This facilitating effect was abolished by either saralasin or benazeprilat (n = 6 for each group). In contrast, in two further groups of patients (n = 6 for each group), in the presence of the beta-blocker propranolol saralasin and benazeprilat did not alter the vasoconstrictor action of the endogenous sympathetic stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)

Humoral and haemodynamic effects of idrapril calcium, the prototype of a new class of ACE-inhibitors, in essential hypertensive patients.

Idrapril is the prototype of a new class of ACE inhibitors, characterised by the presence of a hydroxdmic group. Six untreated in-patients with essential hypertension were given single oral doses of the calcium salt of idrapril, idrapril calcium (200 mg) and placebo according to a double blind, randomised experimental design. Supine and upright blood pressure, heart rate, plasma idrapril serum UCE, active renin and angiotensin II were measured at timed intervals for 24 hours after dosing. Plasma idrapril reached a peak after 2 hours (3.01 microgm x ml(-1)), and by 12 hours the compound had almost disappeared (67 ng x ml(-1)). Derived t1/2 was 1.4-2.2 h. ACE activity was suppressed [from 77.9 to 3.3 after 2 hours and 11.8 after 12 hours nmol(-1) x min(-1) x ml] and angiotensin II production inhibited [from 8.8 to 3.1 (after 1 hour) and 7.5 (after 24 hours) pg x ml(-1)]. Compared to placebo, idrapril calcium significantly lowered both supine blood pressure starting at 4 hours (idrapril calcium 140/93 mmHg; placebo 157/101 mmHg; placebo 147/100 mmHg), and upright blood pressure starting at 3 hours (idrapril calcium 135/95 mmHg; placebo 147/100 mmHg) up to 24 hours (idrapril calcium 132/92 mmHg; placebo 145/100 mmHg). Idrapril calcium appears to be an effective ACE inhibitor in essential hypertension, with a hypotensive action for up to 24 h.

Hemodynamic and humoral effects of low-dose aspirin in treated and untreated essential hypertensive patients.

Aspirin at low doses is used as an inhibitor of platelet aggregation and is frequently administered to essential hypertensive patients with arterial thrombotic complications. However, it is unknown whether aspirin can modify blood pressure values either in treated or untreated hypertensive patients, as described for other non steroidal anti-inflammatory drugs. Thus 30 patients. 10 with mild uncomplicated and untreated essential hypertension, 10 with essential hypertension under chronic treatment with captopril, 50 mg bid, and 10 with essential hypertension under chronic treatment with atenolol, 100 mg oid, received aspirin, 100 mg oid, and the corresponding placebo for one month, according to a double blind randomized cross-over design. At the end of each treatment, blood pressure, heart rate, generated serum thromboxane B2 and urinary excretion of thromboxane B2 and 6 keto prostaglandin F1 alpha and plasma renin activity were measured. Both in treated and untreated essential hypertensive patients, aspirin administration did not affect blood pressure, heart rate and urinary 6 keto prostaglandin F1 alpha, while it significantly reduced serum and urinary excretion of thromboxane B2 and plasma renin activity. In conclusion, while the present data confirm that low doses of aspirin selectively inhibit thromboxane B2 synthesis, they indicate that aspirin at 100 mg oid can be administered to treated and untreated essential hypertensive patients without any harmful effect on blood pressure values.

Vascular renin-angiotensin system and sympathetic nervous system activity in human hypertension.

Experimental data indicate the existence of a vascular tissue renin-angiotensin system in several different vessels from various animal models. Active renin can be locally synthesized into the vessel wall or taken up from circulating plasma to produce vascular angiotensin II. Using the human forearm technique, we produced evidence indicating the release of active and inactive renin and of angiotensin II from the vessels of hypertensive patients. Moreover, the production of vascular angiotensin II seems to be strictly correlated to the circulating renin profile, suggesting the possibility that vascular renin might be at least partially taken up from plasma. To investigate a possible function of the vascular renin-angiotensin system, we studied its interaction with sympathetic neurotransmission in essential hypertensive patients. In line with animal studies, vascular angiotensin II increases the vasoconstriction induced by the stimulation of the sympathetic nervous system through the potentiation of noradrenaline release at a presynaptic level, and this effect seems to be mediated by beta-adrenoceptor activation. This facilitating effect on sympathetic neurotransmission exerted by vascular angiotensin II can be antagonized by both angiotensin II antagonists and angiotensin-converting enzyme inhibitors.

Indirect evidence for vascular uptake of circulating renin in hypertensive patients.

To evaluate whether, in the forearm of hypertensive patients with different circulating renin profiles, local beta-adrenergic receptor-induced production of active renin, plasma renin activity, angiotensin I (Ang I), and angiotensin II (Ang II) was or was not related to the renin profile, we studied four groups of patients: 1) hypertensive patients with primary aldosteronism and suppressed circulating plasma renin activity values (0.15 +/- 0.1 ng Ang I/mL per hour; n = 7), 2) essential hypertensive patients with low (0.47 +/- 0.1 ng Ang I/mL per hour; n = 8) circulating plasma renin activity values, 3) essential hypertensive patients with normal (2.48 +/- 0.52 ng Ang I/mL per hour; n = 8) circulating plasma renin activity value, and 4) renovascular hypertensive patients with high circulating plasma renin activity values (4.16 +/- 2.1 ng Ang I/mL per hour; n = 10). Isoproterenol was infused into the brachial artery, and active renin, plasma renin activity, and Ang I and Ang II forearm balance (venous-arterial differences corrected for forearm blood flow by strain-gauge plethysmography) were measured. Despite a comparable vasodilation, beta-adrenergic stimulation failed to release active renin, plasma renin activity, and Ang I and Ang II in primary aldosteronism. It slightly increased them (except for Ang I) in low renin patients but determined a local production in normal renin and renovascular hypertensive patients. The individual increments in plasma renin activity and Ang II release induced by isoproterenol showed a correlation with the renin profile.(ABSTRACT TRUNCATED AT 250 WORDS)

Activation of sympathetic tone during dipyridamole test.

Cardiac imaging with dipyridamole infusion has been proposed as an exercise-independent tool for the diagnosis of coronary artery disease. Dipyridamole acts through the accumulation of adenosine, which reduces sympathetic tone in vasomotor nuclei of the brainstem and inhibits norepinephrine release in noradrenergic neurons but also activates arterial chemoreceptors. The aim of this study was to assess whether dipyridamole administration (up to 0.84 mg/kg over 10 minutes, a dosage commonly employed for diagnostic testing) may modulate sympathetic activity either directly or indirectly through blood pressure reduction or myocardial ischemia, which may be evoked by dipyridamole infusion and represent two recognized sympathetic stimuli. Twenty patients were studied with infusion combined with two-dimensional echocardiography and 12-lead ECG monitoring. Blood pressure was recorded each minute by a cuff sphygmomanometer. In all patients, we obtained venous blood samples for epinephrine (an index of adrenomedullary catecholamine release) and norepinephrine (an index of neuronal activity) both in resting conditions and at peak dipyridamole, ie, at the first minute after termination of dipyridamole infusion in negative cases or in the presence of obvious ischemia in positive cases (ie, as soon as a regional ventricular dyssynergy or an ST segment depression greater than 0.1 mV appeared). Epinephrine and norepinephrine determinations were made by a high performance liquid chromatography (HPLC) method. After dipyridamole, there was a significant rise in norepinephrine, while epinephrine did not change significantly. Dipyridamole-induced percentage variations of norepinephrine from baseline were not significantly correlated with mean blood pressure changes (r = .1, p = ns) and were of a similar extent in patients with (n = 10) and without (n = 10) dipyridamole-induced ischemia (+68 vs +73 percent, p = ns). Dipyridamole administration provokes an activation of sympathetic tone which can be detected even in the absence of myocardial ischemia and is not related to blood pressure changes. The increased catecholamine release appears to be of neuronal rather than adrenomedullary origin.

Adenosine activates a vascular renin-angiotensin system in hypertensive subjects.

In vitro data indicate that the activation of A2 adenosine receptors increases renin release by the accumulation of cyclic AMP. Because in human forearm vessels beta-adrenergic receptor stimulation causes the local release of renin and angiotensin II through the increase of cyclic AMP, we evaluated in six essential hypertensive subjects whether adenosine can release vascular angiotensin II. Adenosine was infused into the brachial artery at cumulatively increasing doses (0.5, 1.5, and 5 micrograms/100 ml forearm tissue per minute for 5 minutes each) during saline infusion and in the presence of the adenosine antagonist theophylline (100 micrograms/100 ml forearm tissue per minute for 15 minutes), while venous (ipsilateral deep forearm vein) and arterial (brachial artery) angiotensin II (picograms per milliliter) were measured at the end of each infusion period, and forearm angiotensin II net balance (picograms per minute) was calculated by venous-arterial differences corrected for forearm blood flow (strain-gauge venous plethysmography) and hematocrit. In control conditions, adenosine, at higher doses, caused a dose-dependent vasodilation and increased venous angiotensin II without affecting arterial values; therefore, the calculated angiotensin II net balance showed an adenosine-mediated dose-dependent release. Theophylline pretreatment blunted adenosine-mediated forearm blood flow increments and angiotensin II release. The local origin of angiotensin II was further confirmed in another group of six hypertensive subjects in whom the angiotensin converting enzyme inhibitor captopril, locally infused at the rate of 2.5 micrograms/100 ml forearm tissue per minute for 15 minutes, abolished the adenosine-mediated venous angiotensin II increments. Our data indicate that exogenous adenosine can stimulate the production of angiotensin II in the forearm vessels of hypertensive patients.

Atrial natriuretic factor in essential hypertension: echocardiographic and humoral correlates.

Aim of this study was to assess the relationship between plasma concentration of atrial natriuretic factor (ANF) and its two-dimensional echocardiographic (left ventricular mass, left atrium diameter) and humoral (plasma renin and aldosterone) variables in essential hypertension (EH). We evaluated 32 patients with uncomplicated mild to moderate EH and 10 controls. They were studied in the supine position after 7 days of constant dietary sodium intake and were off therapy since at least 3 weeks. ANF values overlapped between EH patients and controls (27.8 +/- 11.5 vs. 19.5 +/- 7.4 pg/ml, p = NS). In EH, no significant correlation was found between ANF values and left ventricular mass (r = 0.29), left atrial diameter (r = 0.04), mean arterial blood pressure (r = 0.26), plasma renin activity (r = 0.00), and aldosterone (r = 0.26). In EH, ANF values overlapped between the 15 patients with hypertrophy and the 17 patients with normal ventricular mass: 30.3 +/- 17 vs. 25.6 +/- 10.6 pg/ms (p = NS). We conclude that there is a substantial overlap in plasma ANF values between mild to moderate uncomplicated EH and controls, and left ventricular hypertrophy is not a major independent stimulus to ANF release in EH.

Doxorubicin cardiotoxicity is associated with alterations of plasma levels of atrial natriuretic factor.

In order to determine the involvement of the atrial natriuretic factor (ANF) in a model of drug-induced cardiomyopathy, the effects of a single or repeated doses of doxorubicin on plasma ANF levels were examined. Female Wistar rats were treated with doxorubicin at two different schedules: a single 10 mg/kg iv dose or multiple 3 mg/kg iv doses once a week for 3 weeks; control groups were given vehicle (isotonic saline, 0.9% NaCl) intravenously. ANF was assayed in plasma by a specific and sensitive radioimmunoassay method and cardiac function was evaluated by monitoring of ECG and hemodynamic parameters. In the doxorubicin single-dose study plasma ANF values were measured during a period of 6 hours after dosing and were found to be significantly decreased at the 180th (12.5 +/- 2.9 pg/ml) and 360th minute (19.4 +/- 1.2 pg/ml) after dosing, compared to vehicle-treated animals (35.1 +/- 5.7 and 37.9 +/- 4.1 pg/ml, 180 and 360th minute, respectively). Rats treated with multiple doses of doxorubicin showed a significant increase in plasma ANF levels at the 21st (88.3 +/- 7.7 pg/ml) and 31st day (61.0 +/- 14.3 pg/ml) of the study compared to vehicle-treated animals at the same time points (41.8 +/- 8.0 and 26.5 +/- 7.2 pg/ml, respectively). At the 42nd day plasma ANF concentration in doxorubicin-treated rats was not significantly different from vehicle-treated rats. In both studies ANF level changes occurred in the setting of acute or chronic doxorubicin-induced cardiac damage, as evidenced by alterations of hemodynamic and ECG parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Vascular renin-angiotensin system and neurotransmission in hypertensive persons.

The existence of a vascular renin-angiotensin system and its role in modulating sympathetic activity were evaluated in forearm arterioles of hypertensive individuals. Isoproterenol (0.03, 0.01, 0.3 microgram/100 ml/min for 5 minutes each; n = 5) was infused into the brachial artery, and active and inactive renin, angiotensin II, and norepinephrine forearm balance (venous-arterial differences corrected for forearm blood flow by strain-gauge plethysmography) were measured. Isoproterenol caused vasodilation and a dose-dependent active and inactive renin, angiotensin II, and norepinephrine outflow, an effect blunted by propranolol (10 micrograms/100 ml/min). To evaluate the role of local angiotensin II on beta-mediated norepinephrine overflow, the experiment was repeated with captopril (2.5 micrograms/100 ml/min for 10 minutes; n = 5), which abolished angiotensin II release and significantly reduced norepinephrine overflow. To test whether angiotensin II facilitates both prejunctional norepinephrine release and its postjunctional action, we evaluated the effect of exogenous angiotensin II, infused into the brachial artery at low concentrations (0.001 microgram/100 ml/min), on forearm vasoconstriction and norepinephrine release induced by endogenous sympathetic activation (application of a lower body negative pressure: -10 and -20 mm Hg for 5 minutes, n = 10) and on the vasoconstrictor effect of local norepinephrine (0.0015, 0.005, 0.015, 0.05, 0.15 micrograms/100 ml/min for 3 minutes each; n = 6). Although angiotensin II increased the vasoconstricting effect and the norepinephrine release induced by lower body negative pressure, it failed to affect norepinephrine-mediated vasoconstriction. Our data indicate the existence in hypertensive individuals of a vascular renin-angiotensin system that seems to modulate sympathetic activity through the presynaptic facilitation of norepinephrine release.