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Biomedical subjects

G Frati

Publications and source records attributed to G Frati.

At least 19 recordsLinked to original sources
PubMed2002

Carnitine inhibits arachidonic acid turnover, platelet function, and oxidative stress.

Carnitine is a physiological cellular constituent that favors intracellular fatty acid transport, whose role on platelet function and O(2) free radicals has not been fully investigated. The aim of this study was to seek whether carnitine interferes with arachidonic acid metabolism and platelet function. Carnitine (10-50 microM) was able to dose dependently inhibit arachidonic acid incorporation into platelet phospholipids and agonist-induced arachidonic acid release. Incubation of platelets with carnitine dose dependently inhibited collagen-induced platelet aggregation, thromboxane A(2) formation, and Ca(2+) mobilization, without affecting phospholipase A(2) activation. Furthermore, carnitine inhibited platelet superoxide anion (O(2)(-)) formation elicited by arachidonic acid and collagen. To explore the underlying mechanism, arachidonic acid-stimulated platelets were incubated with NADPH. This study showed an enhanced platelet O(2)(-) formation, suggesting a role for NADPH oxidase in arachidonic acid-mediated platelet O(2)(-) production. Incubation of platelets with carnitine significantly reduced arachidonic acid-mediated NADPH oxidase activation. Moreover, the activation of protein kinase C was inhibited by 50 microM carnitine. This study shows that carnitine inhibits arachidonic acid accumulation into platelet phospholipids and in turn platelet function and arachidonic acid release elicited by platelet agonists.

Arachidonic Acid↗
PubMed2002

Surgical treatment of abdominal aortic aneurysms associated with aortic valve incompetence: strategies and outcomes.

BACKGROUND: The exact incidence of associated aortic valve incompetence (AVI) and abdominal aortic aneurysm (AAA) in the general population is not known. In recent years, we have observed this association with increasing frequency. This observation is probably due to the extensive preoperative screening of the cardiac and vascular status of patients who are candidates for surgical procedures. The choice of the optimal surgical strategy is needed to achieve low operative morbidity and mortality. The present study reviews our experience with a subset of patients suffering the association of AVI and large AAA. Surgical strategy, clinical management and outcome are presented. METHODS: Between January 1982 and May 2000, 76 patients with the association of AAA and AVI have been evaluated in our institution. Forty-four patients have been treated for both AAA and aortic valve (AV) regurgitation. These patients have been divided into three groups on the basis of the surgical strategy adopted. Group 1: combined procedure (16 patients); group 2: AAA repair prior to AV surgery (nine patients); group 3: AV surgery prior to aneurysm repair (19 patients). RESULTS: Hospital mortality was 4.5% (two patients); overall mortality was 6.8% (three patients). CONCLUSIONS: In patients with AAA and AVI, an accurate and complete preoperative evaluation is essential. Surgical strategy should be individualized on the basis of the cardiac preoperative status.

Adult↗
PubMed2002

Emergency management of spontaneous coronary artery dissection.

Six cases of spontaneous coronary arteries dissection are reported. In one patient, triple vessel spontaneous coronary artery dissection was identified. Another patient presented spontaneous left main coronary artery dissection. In one case we found the spontaneous dissection of the left anterior descending artery associated with distal aortic arch dissection. These conditions are very rare and may present a surgical dilemma. Causative factors and underlying pathology are clarified. Prompt diagnosis and surgical intervention is safe and effective. Early recognition of left main coronary artery dissection or three-vessel dissection is essential because urgent coronary artery bypass grafting may be life saving.

Adult↗
PubMed2002

Accessory mitral valve leaflet in an adult with coronary artery disease.

Accessory mitral valve leaflet is a very rare cause of left ventricular outflow tract obstruction. We report a patient presenting this cardiac abnormality who undergone cardiac surgery. A 60-year-old man, presented coronary artery disease and moderate left ventricular tract obstruction due to accessory mitral valve leaflet. The accessory mitral valve leaflet had the typical morphology of a parachute-shaped attached partially to the anterior mitral valve leaflet, with chordae tendinae attached to: 1) an accessory papillary muscle inserted at the free-wall closed to the apex; 2) interconnected with the chordae tendinae of the anterior mitral valve leaflet; 3) a second accessory papillary muscle inserted to the interventricular septum. He underwent successful coronary revascularization of 2 vessels and accessory leaflet excision. A review of 21 cases with accessory mitral valve leaflet is reported.

Cardiac Catheterization↗
PubMed2001

Cardiomyocytes induce endothelial cells to trans-differentiate into cardiac muscle: implications for myocardium regeneration.

The concept of tissue-restricted differentiation of postnatal stem cells has been challenged by recent evidence showing pluripotency for hematopoietic, mesenchymal, and neural stem cells. Furthermore, rare but well documented examples exist of already differentiated cells in developing mammals that change fate and trans-differentiate into another cell type. Here, we report that endothelial cells, either freshly isolated from embryonic vessels or established as homogeneous cells in culture, differentiate into beating cardiomyocytes and express cardiac markers when cocultured with neonatal rat cardiomyocytes or when injected into postischemic adult mouse heart. Human umbilical vein endothelial cells also differentiate into cardiomyocytes under similar experimental conditions and transiently coexpress von Willebrand factor and sarcomeric myosin. In contrast, neural stem cells, which efficiently differentiate into skeletal muscle, differentiate into cardiomyocytes at a low rate. Fibroblast growth factor 2 and bone morphogenetic protein 4, which activate cardiac differentiation in embryonic cells, do not activate cardiogenesis in endothelial cells or stimulate trans-differentiation in coculture, suggesting that different signaling molecules are responsible for cardiac induction during embryogenesis and in successive periods of development. The fact that endothelial cells can generate cardiomyocytes sheds additional light on the plasticity of endothelial cells during development and opens perspectives for cell autologous replacement therapies.

Animals↗
PubMed2001

Heart-targeted overexpression of caspase3 in mice increases infarct size and depresses cardiac function.

Up-regulation of proapoptotic genes has been reported in heart failure and myocardial infarction. To determine whether caspase genes can affect cardiac function, a transgenic mouse was generated. Cardiac tissue-specific overexpression of the proapoptotic gene Caspase3 was induced by using the rat promoter of alpha-myosin heavy chain, a model that may represent a unique tool for investigating new molecules and antiapoptotic therapeutic strategies. Cardiac-specific Caspase3 expression induced transient depression of cardiac function and abnormal nuclear and myofibrillar ultrastructural damage. When subjected to myocardial ischemia-reperfusion injury, Caspase3 transgenic mice showed increased infarct size and a pronounced susceptibility to die. In this report, we document an unexpected property of the proapoptotic gene caspase3 on cardiac contractility. Despite inducing ultrastructural damage, Caspase3 does not trigger a full apoptotic response in the cardiomyocyte. We also implicate Caspase3 in determining myocardial infarct size after ischemia-reperfusion injury, because its cardiomyocyte-specific overexpression increases infarct size.

Animals↗
PubMed2001

Total mesorectal excision and low rectal anastomosis for the treatment of rectal cancer and prevention of pelvic recurrences.

HYPOTHESIS: Total mesorectal excision lowers the rate of pelvic recurrence and positively affects the survival after surgical treatment of rectal cancer. DESIGN: Case series. SETTING: Tertiary care university hospital. PATIENTS: Fifty-three consecutive patients were admitted with curative intent to surgery at the First Department of Surgery of the University of Rome "La Sapienza," Rome, Italy, with diagnoses of rectal carcinoma. The mean follow-up was 68.9 months; follow-up was complete for all patients who entered the trial. INTERVENTIONS: Low anterior resection and total mesorectal excision were performed in all cases, regardless of the location of the rectal cancer. A straight mechanical colorectal anastomosis was performed on a rectal stump, never exceeding 5 cm. No kind of adjuvant therapy was given. Mesorectum and open rectum were studied by serial transverse section at 5-mm intervals. A search for depth of penetration and distal intramural extension of the tumor was made. Lymph nodes were detected by clearing method, and nodal metastases (NM) and nonnodal metastases (NNM) were recorded as situated proximally, distally, or at the level of the tumor. RESULTS: There was no postoperative mortality. Clinical and radiologic leaks occurred in 2 and 4 patients, respectively. Mean disease-free survival was 65.9 months. Pelvic recurrence occurred in 5 patients (9%). Overall 5-year survival rate was 75%. Involvement of mesorectum by NM and NNM was detected in 27 and 24 cases, respectively. Both NM and NNM were found to be distal in 33% and 40% of cases, respectively. CONCLUSIONS: Microscopic spread to the distal mesorectum may exceed the intramural spread of rectal cancer. Failure to perform total mesorectal excision leaves a potentially residual disease in the distal mesorectum, thus predisposing the patient to pelvic recurrence.

Adenocarcinoma↗
PubMed2001

Restoration of patency after apparent occlusion of the lambda-graft's right branch.

The "string sign" is a physiological and reversible response of the internal mammary artery (IMA) anastomosed to a moderately stenotic coronary artery. We describe a patient who presented postoperatively with a string sign phenomenon of the right branch of the lambda-composite graft. The graft regained full patency 32 months after the surgical procedure with progression of the native coronary artery stenotic lesion. This case demonstrates that under specific conditions, such as the progression of native coronary artery disease, a no-flow composite graft employing IMAs can only regain patency and functional status in the same way as in situ IMAs. These findings confirm that the IMA remains the conduit of choice not only for its long-term patency, but also for its physiological adaptation characteristics.

Adaptation, Physiological↗
PubMed2001

Lambda graft with the radial artery or free left internal mammary artery anastomosed to the right internal mammary artery: flow dynamics.

BACKGROUND: The aim of this study was to evaluate the outcome and flow dynamics of the lambda graft configuration, relative to a second arterial graft. METHODS: From 1998 to 2000, 47 patients (mean age 55.5 +/- 4.7 years) with triple-vessel disease underwent arterial revascularization using the lambda graft. The in situ left internal mammary artery (LIMA) and right internal mammary artery (RIMA) were anastomosed to the left anterior descending (LAD) and obtuse marginal arteries, respectively. In 21 patients (group I) presenting proximal or middle-third LAD or right coronary (RC) arterial stenoses, the lambda graft was constructed by anastomosing the distal LIMA, as a free LIMA graft, to the RC and proximally to the in situ RIMA. In the other 26 patients (group II) presenting with middle-distal third LAD or RC arterial stenoses, the radial artery (RA) was used to construct the lambda graft. All patients underwent transthoracic echo color Doppler before and after an adenosine test at 1 week and 3 months after operation. RESULTS: There were no hospital deaths. Overall, 47 lambda grafts were constructed. There was no difference between baseline and maximal flows and coronary flow reserve (CFR) between groups. CFR at IMA stems increased in both groups within 3 months versus 1 week [(LIMA)CFR = 2 +/- 0.3 vs 2.3 +/- 0.3 (p = 0.002) and (RIMA)CFR = 2.2 +/- 0.4 vs 2.5 +/- 0.3 (p = 0.009) in group I, and (LIMA)CFR = 2.12 +/- 0.33 vs 2.4 +/- 0.35 (p = 0.005) and (RIMA)CFR = 2.17 +/- 0.32 vs 2.52 +/- 0.26 (p = 0.001) in group II]. At 3 months versus 1 week, the (RIMA)diameter(i) (mm) at rest was 1.69 +/- 0.32 versus 1.48 +/- 0.2 (p = 0.015) in group I and 1.66 +/- 0.3 versus 1.47 + 0.2 (p = 0.01) in group II. At 6 +/- 2.4 months, all patients were free of angina. CONCLUSIONS: These data, almost identical for free LIMA and RA to RIMA using the lambda graft, demonstrate that RIMA flow reserve is adequate for multiple coronary anastomoses irrespective of the second arterial graft.

Arteries↗
PubMed2001

Beating heart myocardial revascularization on extracorporeal circulation in patients with end-stage coronary artery disease.

OBJECTIVES: To evaluate in a cohort of ESCAD patients (pts) the effects of on-pump/beating-heart versus conventional CABG in terms of early and mid-term survival and morbidity and LV function improvement. METHODS: Between January 1993 and December 2000, 78 (Group I) ESCAD pts underwent on-pump/beating-heart surgery. Mean age in Group I was 66.2+/-6 (58-79), NYHA and CCS class were 3.2+/-0.6 and 3.3+/-0.4 respectively, Myocardial viability index 0.69+/-0.1 (%), LVEF (%) 24.8+/-4, LVEDP (mmHg) 28.1+/-5.8 and LVEDD(mm) 69.5+/-6. Group II consisted in 78 ESCAD patients undergoing conventional CABG selected in a randomized fashion from an age, sex, and LVEF corrected group of patients. Mean age in Group II was 65.7+/-5 (57-78), NYHA 3.1+/-0.7, CCS 3.4+/-0.8, LVEF(%) 25+/-5, LVEDP(mmHg) 27.9+/-4.4 and LVEDD(mm) 69.2+/-7.2. RESULTS: Postoperatively, 5(7.7%) patients died in Group I versus 7(11.5%) patients in Group II (P>0.1). CPB time resulted to be in Group II patients (P=0.001) and the mean distal anastomoses per patient was similar between groups (P=Ns). Perioperative AMI (P=0.039), LCOS (P=0.002), necessity for ultrafiltration (P=0.018) and bleeding>1000 ml (P=0.029) were significantly higher in Group II. None of the Group I patients underwent surgical revision for bleeding versus 8(10.3%) patients in Group II (P=0.011). At 6 months after surgery, the LV function improved significantly in Group I patients, demonstrated by an increased LVEF=27.2+/-4(%)(P=0.001), lower LVEDP=26.4+/-3(mmHg)(P=0.029) and LVEDD=67+/-4(mm) (P=0.004) instead of a lower LVEDD=66.8+/-6(mm)(P=0.032) versus the preoperative data in Group II. The actuarial survival at 1, 3 and 5 yr were 90, 82 and 71% in Group I and 89, 83 and 74% in Group II (P=Ns). CONCLUSION: In ESCAD patients who may poorly tolerate cardioplegic arrest, on-pump/beating-heart CABG may be an acceptable alternative associated with lower postoperative mortality and morbidity. Such a technique offers a better myocardial and renal protection associated with lower postoperative complications due to intraoperative hypoperfusion.

Aged↗
PubMed2001

Respiratory dysfunction after coronary artery bypass grafting employing bilateral internal mammary arteries: the influence of intact pleura.

OBJECTIVE: To evaluate the role of intact pleurae regarding the postoperative respiratory functional status in patients undergoing coronary revascularization employing both internal mammary arteries (IMAs), according to the pedunculated or skeletonized technique (SKT) with opened or intact pleurae. MATERIALS AND METHODS: Using both IMAs, 299 patients underwent elective coronary revascularization. They were randomized and divided into group I (n=82, undergoing IMA harvesting according to the SKT without opening the pleurae); group II (n=186, undergoing IMA harvesting according the pedunculated technique with open pleurae); and group III (n=31, undergoing IMA harvesting according the SKT with incidentally opened pleurae). There were no differences regarding the preoperative patient characteristics and the anaesthetic and surgical management. RESULTS: There were two deaths in group I versus seven in group II and one in group III (P=ns). The number of total arterial myocardial revascularization and arterial composite grafts was significantly higher in groups I and III than in group II, (P<0.001 and P<0.005, respectively). The incidence of postoperative complications was similar between groups. Blood loss of >1000 ml was significantly higher in group II than group I (P<0.028); but the incidence of re-thoracotomy and blood transfusion was similar between groups. The mechanical ventilation time was significantly higher in groups II and III versus group I (P<0.018 and P<0.02, respectively). The incidence of prolonged ventilation (>24 h), pleural effusion, thoracocentesis and atelectasis, resulted in being significantly higher in group II than group I. The incidence of thoracocentesis was significantly higher in group III than group I. The pain score and analgesic requirements at 1-12 h after awakening were significantly higher in groups II and III versus group I, becoming similar after the chest tubes were removed. PaO(2) was significantly higher, and PaCO(2) and FiO(2) were significantly lower in group I than groups II and III at 1 and 4 h before extubation and at 1 and 4 h after extubation. PaO(2) and PaCO(2) became similar between groups at the 5th postoperative day. CONCLUSIONS: According to our results, we may conclude that pleural integrity has beneficial effects on the respiratory functional status after coronary revascularization using both IMAs. A meticulous and more careful IMA harvesting approach significantly reduces the postoperative morbidity regarding the pulmonary functional status, and as a consequence, reduces the hospital costs.

Blood Loss, Surgical↗
PubMed2001

Urgent surgical revascularization of unstable angina. Influence of double mammary arteries.

OBJECTIVE: Aim of this study was to evaluate retrospectively: (1) the outcome in patients with unstable angina (UA) refractory to the medical therapy undergoing urgent-emergent CABG; (2) the influence of both IMAs employment. PATIENTS AND METHODS: Between January 1995 and July 2000, 576 (28.5%) consecutive patients with UA underwent CABG procedure. 182 (31.6%, Group I) patients, presenting unstable hemodynamic or angina pectoris refractory to the maximal medical therapy, underwent urgent/emergent CABG. 397 (68.4%, Group II) patients, after the maximal medical therapy did not present angina's episodes or ECG alterations and underwent elective CABG procedure. Preoperative data were similar in the two groups. Both IMAs were used in 68 (37.4%) patients of I and 152 (38%) of II (P>0.05) to left side revascularization. RESULTS: CAD extension was greater in Group I: 45 (24.7%) patients presented ischemia in >1 area vs 53 (13.5%) in II (P<0.001). Incidence of anteroseptal ischemia resulted significantly higher in I (P=0.017); left main coronary artery stenosis was present in 68 (37%) patients in I vs 108 (27%) in II (P=0.01). LV function resulted significantly depressed in I, demonstrated by a significantly lower LVEF (P<0.001), higher NYHA class (P<0.001) and preoperative incidence of IABP (P<0.001). Intraoperative data analysis did not reveal any difference between groups. Hospital mortality was 13 (7%) and 21 (5.3%) patients in I and II respectively (P=ns). Multivariate analysis of all preoperative and intraoperative variables revealed the age >65 years (P=0.01), congestive heart failure (P<0.001), LVEF<35% (P=0.03), >1 ischemic area (P=0.02) as strong predictors for poor overall survival, and LIMA (P=0.006) and both IMAs (P=0.001) as strong predictors for good overall survival. Actuarial survival at 1, 3 and 5 years resulted to be 98.5, 96.5 and 90% in I and 99, 96 and 92% in II (P=ns). CONCLUSION: CABG has been associated with acceptable outcome in patients with UA which should be applied soonest possible in patients refractory to medical treatment. Total coronary revascularization and employment of both IMAs for left myocardial side are associated with low operative risk and incidence of complications, permit to have acceptable short and long-term outcome in this pool of patients.

Aged↗
PubMed2001

Proximal aortic dissection with coronary malperfusion: presentation, management, and outcome.

BACKGROUND: Acute myocardial ischemia and infarction due to retrograde dissection of the aortic root reaching the coronary ostia is a potentially fatal condition. Surgical treatment of these patients relies on the re-establishment of an adequate coronary blood flow and on the rescue of jeopardized myocardium. This article reports the results of a selected group of 24 patients with type A acute aortic dissection and coronary artery dissection. We review our experience and illustrate our approach to this condition, which evolved over a 15-year period. METHODS: Between July 1985 and March 2000, 24 patients from a total of 211 (11.3%) treated for acute type A aortic dissection had dissection of at least one of the coronary ostia. There were 14 men and 10 women. The mean age was 65.5 years (median 61.7; range 41-78 years). The right coronary artery was involved in 11 patients, the left in 4 patients, and both coronary arteries in 9 patients. At admission, 16 patients had Q waves (66%), inferior in 6 (25%) and anterior, lateral, septal, or posterior in 10 (41%). All procedures were done on an emergency basis within 10 hours (median 4 hours) after initial chest pain and within 2 hours after the patient's arrival. RESULTS: Hospital mortality was 20% (5 patients); 3 patients could not be weaned from cardiopulmonary bypass and died intraoperatively, and 2 patients died postoperatively of low cardiac output. CONCLUSIONS: As illustrated in this study, direct coronary repair is a safe alternative to bypass grafting. Aggressive myocardial resuscitation together with early operation is a key factor in the management of these patients.

Adult↗
PubMed2001

Perioperative use of tirofiban hydrochloride (Aggrastat) does not increase surgical bleeding after emergency or urgent coronary artery bypass grafting.

BACKGROUND: The platelet glycoprotein IIb/IIIa inhibitor tirofiban hydrochloride improves outcome in patients with acute coronary syndrome. Nevertheless, a considerable number of patients require emergency or urgent coronary artery bypass grafting and may be at increased risk of postoperative bleeding after treatment with this molecule. The aim of this study is to evaluate the incidence of bleeding complications among patients undergoing bypass grafting after treatment with tirofiban. METHODS: We investigated the influence of the molecule on postoperative bleeding after cardiac surgery, comparing 2 groups of patients undergoing emergency or urgent coronary artery bypass grafting: group A (n = 20) received tirofiban, and group B (n = 68) received conventional therapy with intravenous heparin up until the operation. A total of 88 patients underwent coronary artery bypass surgery within 2 hours of ceasing the hemodynamic study. Clinical outcome, chest tube outputs, bleeding complications, transfusion requirements, platelet and hemoglobin counts, and clinical complications were examined. RESULTS: Bleeding differences were noted between the 2 groups at 8, 16, and 24 hours postoperatively. The incidence of blood, platelet, and fresh frozen plasma transfusions was higher in the control group. Postoperative thrombocytopenia was preserved in group A (199.5 +/- 70.4 vs 150.6 +/- 33.4 10(3)/mL, P <.01). No significant differences were noted between the 2 groups in the incidence of perioperative myocardial infarction, but significant differences were noted in enzyme levels, length of stay in the intensive care unit, and length of stay in the hospital. No deaths were observed. Hospital morbidity was increased in group B because of factors that were not apparently linked with tirofiban infusion. CONCLUSIONS: Patients may safely undergo coronary artery bypass surgery after treatment with tirofiban hydrochloride. This molecule, administered in the immediate preoperative period, has no adverse clinical effects and does not seem to negatively influence the incidence of perioperative myocardial infarction. Although extracorporeal circulation can modify platelet numbers and function, our ongoing data could show significant reduction in the loss of platelets induced by cardiopulmonary bypass, minor postoperative bleeding, and a minor transfusion requirement in general.

Blood Transfusion↗
PubMed2001

Mutated p21/WAF/CIP transgene overexpression reduces smooth muscle cell proliferation, macrophage deposition, oxidation-sensitive mechanisms, and restenosis in hypercholesterolemic apolipoprotein E knockout mice.

We have investigated whether by introducing a mutated p21 cyclin-dependent kinase inhibitor through a standard type 5 adenovirus (Ad), it would be possible to interfere with restenosis in hypercholesterolemic apolipoprotein E knockout mice. Restenosis is a clinically relevant, undesired effect of percutaneous transluminal coronary angioplasty (PTCA). A critical event underlying restenosis is smooth muscle cell (SMC) proliferation leading to neointimal formation and vessel reocclusion. Recent data demonstrated that it is possible to reduce restenosis by introducing various genes blocking the cell cycle through Ad vectors. Nonetheless, most experiments were conducted in the healthy carotid artery of rat, which is far from the condition of human disease. Therefore, we investigated whether antiproliferative or proapoptotic genes affect restenosis in a model of atherosclerosis closer to clinical settings. Ad-mutated(m)-p21WAF/CIP1 transgene overexpression induces a significant reduction of restenosis in hypercholesterolemic apolipoprotein E knockout mice subjected to injury of common carotid artery. This was associated with reduced SMC density and proliferation, macrophage deposition, and oxidation-sensitive mechanisms. Treatment with p21/WAF also enhanced TUNEL positivity of arterial cells. We show that in an experimental model of atherosclerosis, braking the cell proliferation through increased vascular apoptosis and reduced oxidation-sensitive signal transduction and macrophage accumulation can significantly ameliorate the deleterious effects of vascular injuries similar to those that occur during PTCA and related procedures.

Adenoviridae↗
PubMed2001

Impaired insulin-like growth factor I vasorelaxant effects in hypertension.

Insulin-like growth factor I (IGF-I) can be considered a factor potentially involved in arterial hypertension not only for its growth-promoting features but also for its effects on vascular tone. Nevertheless, the actions of the hormone on vascular reactivity are still unexplored in hypertension. Therefore, the vasodilation induced by increasing doses of IGF-I and the modulation of norepinephrine vasoconstriction induced by low levels of the hormone were tested on aortic rings of spontaneously hypertensive and normotensive rats. The results indicate that the vasodilation evoked by IGF-I is impaired in hypertensive rats (Delta% of maximal vasorelaxation, 30+/-1 versus 41+/-1; P<0.01), and after the removal of endothelium or the inhibition of endothelial NO synthase, the vasodilation evoked by the hormone was blunted in both rat strains and became similar between hypertensive and normotensive rats (Delta% of maximal vasorelaxation, 21+/-1 versus 20+/-1; P=NS). Moreover, IGF-I does not show any effect on norepinephrine vasoconstriction in hypertensive rats, and this alteration may depend on the lack of sensitizing effect exerted by IGF-I on alpha(2)-adrenergic-evoked NO vasorelaxation. The defect in IGF-I vascular action is also present in young spontaneously hypertensive rats (age 5 weeks). In conclusion, our data demonstrate that IGF-I vasorelaxant properties are impaired in spontaneously hypertensive rats, suggesting that such defect may play a causative or permissive role in the development of hypertensive conditions.

Animals↗