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Biomedical subjects

R Russo

Publications and source records attributed to R Russo.

At least 37 records · Page 2Linked to original sources

Single photon emission computed tomography scanning in childhood systemic lupus erythematosus.

OBJECTIVE: To determine the role of central nervous system (CNS) perfusion scanning in detecting CNS disease in childhood onset systemic lupus erythematosus (SLE) and serial single photon emission computed tomography (SPECT) scans in monitoring CNS disease activity in childhood. METHODS: The charts of 108 patients with a confirmed or suspected diagnosis of SLE during the period February 1987 to June 1992 were reviewed. Twenty patients with a diagnosis of CNS SLE and 10 patients without CNS involvement had at least one SPECT scan. Patients were divided into (a) focal CNS SLE, when there were clinical manifestations that could be attributed to localized lesions of the CNS (6 patients); and (b) diffuse CNS SLE, when there was a global defect in CNS function including organic brain syndrome, psychosis, and depression (14 patients). If a patient had both diffuse and focal CNS disease that patient was designated as having diffuse disease. Forty-three patients with a diagnosis other than SLE comprised our non-SLE control group. RESULTS: SPECT scans were performed in 20 patients with acute CNS involvement. In patients with acute diffuse CNS disease, diffuse patchy areas of hypoperfusion were seen in 86% of patients at presentation of the CNS event. In the focal CNS disease subgroup, 33% of patients had an abnormal scan at CNS presentation. In these patients focal rather than diffuse abnormalities were seen. Eight patients with diffuse CNS SLE had at least one followup study at intervals ranging from 1 month to 3 years after initial scan. In 50% of these patients with diffuse CNS involvement, improvement in their abnormal scan correlated with clinical improvement, while in the other 50% clinical improvement was not associated with SPECT scan improvement. The most common abnormal SPECT scan pattern in patients with CNS SLE was one of widespread multiple small areas of decreased uptake at multiple sites, suggestive of generalized patchy hypoperfusion. Although SPECT scans were sensitive to the presence of CNS disease, the diffuse hypoperfusion was not specific for clinically detectable CNS involvement. In patients with SLE, a diffusely abnormal scan had a specificity of 69% and a likelihood ratio of 2.2 to correctly detect overt diffuse CNS disease. CONCLUSION: Although we found that SPECT scanning was a highly sensitive method, it was not a specific method in correctly diagnosing diffuse CNS SLE in children. However, the presence of an abnormal SPECT scan in SLE patients with no history of overt CNS SLE may suggest that subclinical CNS disease may be more common in children than previously suggested.

Adolescent

[Maternal attitude and psychophysical adaptation of women undergoing primary and secondary cesarean section].

BACKGROUND: The increase of cesarean sections, which is typical of the most industrialised countries, resulted in a higher rate of repeat cesarean sections. The previous CS is the main indication for cesarean delivery. The purpose of this study is to compare women who had a primary cesarean with women who had a repeat cesarean section in order to assess their different emotional reactions as well as their psychophysical consequences. METHODS: A questionnaire was administered to 36 patients who had a primary cesarean section and to 34 patients who had a repeat cesarean section, 6-12 months after birth. All these women were similar for age and gestational age of the birth. RESULTS: Results underline that patients are more disposed to accept the operation in repeat cesarean rather than in primary cesarean. Women who have a repeat cesarean section are more likely to accept this kind of delivery since the beginning, with positive effects on their postoperative course. Women who have a repeat cesarean section face more serenely not only prenatal but also post-natal period and show less serious psychophysical sequelae with respect to primary cesarean section because of their previous experience. CONCLUSIONS: As a result, an appropriate psychological support coupled with adequate information can reduce discomfort in cesarean patients.

Adaptation, Physiological

[Clinical use of leuprolide acetate depot in a group of gynecologic patients in the preoperative period].

BACKGROUND: The authors examined 33 patients with symptomatic uterine leiomyomas due to undergo total hysterectomy in order to evaluate the effects of treatment with GnRH analogues on leiomyoma and estrogen and progesterone receptors. METHODS: The patients were divided into two groups: one group was treated with leuprolide acetate (Group A) and the other did not receive treatment (Group B). RESULTS: A significant reduction in the volume of leiomyomas and estrogen and progesterone receptors was noted in patients in Group A. CONCLUSIONS: Treatment with GnRH analogues therefore represents a valid aid for patients with uterine leiomyomas and sideropenic anemia awaiting surgery.

Adult

Effects of recombinant human growth hormone on muscle protein turnover in malnourished hemodialysis patients.

To assess the effect of recombinant human growth hormone (rhGH) on muscle protein metabolism in uremic patients with malnutrition, forearm [3H]phenylalanine kinetics were evaluated in six chronically wasted (body weight 79% of ideal weight) hemodialysis (HD) patients in a self-controlled, crossover study. Forearm protein dynamics were evaluated before, after a 6-wk course of rhGH (5 mg thrice weekly) and after a 6-wk washout period. After rhGH: (a) forearm phenylalanine net balance--the difference between phenylalanine incorporation into and phenylalanine release from muscle proteins--decreased by 46% (-8+/-2 vs. -15+/-2 nmol/min x 100 ml at the baseline and -11+/-2 after washout, P < 0.02); (b) phenylalanine rate of disposal, an index of protein synthesis, increased by 25% (25+/-5 vs. 20+/-5 at the baseline and 20+/-4 after washout, P < 0.03); (c) phenylalanine rate of appearance, an index of protein degradation, was unchanged (33+/-5 vs. 35+/-5 at the baseline and 31+/-4 after washout); (d) forearm potassium release declined (0.24+/-0.13 vs. 0.60+/-0.15 microeq/min at the baseline, and 0.42+/-0.20 microeq/min after washout P < 0.03); (e) changes in the insulin-like growth factor binding protein (IGFBP)-1 levels and insulin-like growth factor-I (IGF-I)/IGFBP-3 ratios accounted for 15.1% and 47.1% of the percent variations in forearm net phenylalanine balance, respectively. Together, these two factors accounted for 62.2% of variations in forearm net phenylalanine balance during and after rhGH administration. These data indicate: (a) that rhGH administration in malnourished hemodialysis patients is followed by an increase in muscle protein synthesis and by a decrease in the negative muscle protein balance observed in the postabsorptive state; and (b) that the reduction in net protein catabolism obtained with rhGH can be accounted for by the associated changes in circulating free, but not total, IGF-I levels.

Adult

Diagnostic value of multimodal evoked potentials in HIV-1 infected children.

Evoked potentials (EP) help guide the diagnosis of central nervous system involvement in demyelinating pathologies regarding both children and adults, and in human immunodeficiency virus-1 (HIV-1) correlated pathologies only in regard to adult patients. EP have been shown to be useful in highlighting early signs of the disease. We therefore studied EP in HIV-1 infected children with the aim of verifying the association of results with disease progression, clinical signs and electroencephalogram, and individualizing the most reliable test. Thirty-six patients (20 male and 16 female subjects, age range: 10 months to 12 years) belonging to a group of 45 symptomatic subjects seen at the Pediatric Department were included into the study from November 1991 to December 1994. Ten presented with neurological signs as of disease onset, eight others developed encephalopathy during the follow-up. One hundred seventeen EP, i.e., 27 pattern visual, 64 flash visual and 26 brain stem auditory EP, were recorded. Univariate statistical analysis using the Wilcoxon-Mann-Whitney U test and Student's t test was done. As a whole, we found 22.5% of abnormal EP in subjects without neurological signs and 28.3% in subjects with neurological signs. Results that were obtained suggested a close relationship between both the pattern of visual and brain stem auditory EP exams and disease progression.

Acquired Immunodeficiency Syndrome

Gut lavage IgG and interleukin 1 receptor antagonist:interleukin 1 beta ratio as markers of intestinal inflammation in children with inflammatory bowel disease.

BACKGROUND: Whole gut lavage is currently used as preparation before radiological or endoscopic examination of the large bowel. AIM: To validate the gut lavage technique for the assessment of mucosal inflammation, by measuring intestinal IgG and interleukin 1 beta (IL-1 beta) in the fluid obtained. PATIENTS: Sixteen children with Crohn's disease (CD), 14 with ulcerative colitis (UC), and 22 age matched controls. METHODS: Isotonic, non-absorbable polyethylene glycol based lavage solution was given orally or by nasogastric tube. Clear fluid was collected, filtered, and treated with protease inhibitors. IgG, IL-1 beta and IL-1-receptor antagonist (IL-1-ra) were measured by sandwich enzyme linked immunosorbent assay (ELISA). RESULTS: In patients with UC and CD, IgG and IL-1 beta levels were significantly (p < 0.001) higher than in controls. A positive correlation (p < 0.05) was found with disease activity scores. IL-1-ra levels were not significantly different in UC and CD, when compared with controls, but the IL-1-ra:IL-1 beta ratio was significantly (p < 0.01) lower in patients with UC and CD, and negatively (p < 0.001) correlated with IgG levels in lavage fluid. CONCLUSIONS: Gut lavage fluid IgG and IL-1 beta levels and IL-1-ra:IL-1 beta ratio may provide objective discrimination between active and inactive disease in children with inflammatory bowel disease.

Adolescent

Impairment in dating and retrieving remote events in patients with early Parkinson's disease.

Remote memory has been studied in a group of 25 non-demented patients with Parkinson's disease and their performance has been compared with that of 22 healthy control subjects. Only patients who scored > or = 27 on the mini mental state examination and with no anticholinergic treatment were included in the sample. A remote memory questionnaire was given, to evaluate memory for public events that occurred from 1966 to 1990. Each event was probed with five questions concerning its content and one for the date. Compared with healthy subjects, patients with Parkinson's disease were significantly impaired both in recalling the content and in dating remote events. These results support the claim that remote memory in patients with Parkinson's disease is disrupted independently of dementia. This impairment might result from a dysfunction at the level of the circuit connecting the basal ganglia to the frontal lobes.

Adult

Effects of high-cholesterol and atherogenic diets on vascular relaxation in spontaneously hypertensive rats.

Hypercholesterolemia is associated with more rapid development of atherosclerosis, and hypertension is frequently associated with abnormal vascular function. Therefore, to investigate the role of hypercholesterolemia and hypertension on vascular function, we studied three groups of male rats (aged 6 wk): normotensive Wistar-Kyoto rats (WKY) as a control group and spontaneously hypertensive rats (SHR) receiving either standard diet (SD; SHR-SD) or high-cholesterol (1%) diet (ChD; SHR-ChD). Vascular reactivity was tested on isolated aortic rings at 4 wk and at 3 and 6 mo of diet. At 3 mo, endothelium-dependent relaxation to acetylcholine (ACh) and ADP was significantly reduced in SHR-ChD but not in SHR-SD compared with WKY. At 6 mo, relaxations to ACh were further impaired in both SHR groups compared with WKY. Endothelium-independent vasodilation to nitroglycerin (NTG) was not different in the three groups of animals throughout 6 mo of diet. In additional experiments, we evaluated vascular reactivity in rats fed with ChD enriched with an excess of vitamin D [atherogenic diet (AD)] capable of producing vascular atherosclerotic lesions. In particular, we studied three additional groups of WKY and SHR rats fed with SD, AD, or AD plus a nonhypotensive dose of the calcium antagonist nitrendipine (Nit). Vasodilation to ACh and ADP was significantly blunted in WKY-AD compared with WKY-SD, whereas it was partially improved in WKY-Nit. There were no differences in endothelium-independent relaxation to NTG in the three WKY groups. In contrast, SHR-AD showed a marked reduction of endothelium-dependent and -independent vasodilation, but only endothelium-dependent vasodilation was preserved by addition of Nit to the diet. These data suggest that the development of vascular dysfunction in rat genetic hypertension is accelerated by ChD, in absence of detectable vascular lesions. Our study also shows that AD alters both vascular smooth muscle and endothelium-dependent relaxation. Low doses of Nit partially preserve endothelium-dependent vasodilation but do not affect the impairment of smooth muscle function in these rats.

Animals

Opposite feedback control of renin and aldosterone biosynthesis in the adrenal cortex by angiotensin II AT1-subtype receptors.

The aims of this study were to identify whether tissue renin is regulated by a negative-feedback mechanism produced by locally generated angiotensin (Ang II) in the adrenal cortex and to detect the pathway of Ang II modulation. For this purpose, in 36 12-week old, salt-restricted, nephrectomized Sprague-Dawley rats, we studied the effects of the Ang II AT1-subtype receptor antagonist losartan and of the Ang II AT2-subtype receptor antagonist PD123319 on renin mRNA and activity, aldosterone synthase mRNA, and AT1a-, AT1b-, and AT2-subtype receptor expression in the adrenal cortex. Ten additional rats, kept on a regular diet and then nephrectomized, were also studied. In salt-restricted, nephrectomized rats, losartan administration caused increases of adrenal renin mRNA (P<.05) and activity (P<.05) and a concomitant reduction of aldosterone synthase mRNA (P<.05). In addition, after losartan AT1b, receptor mRNA was reduced (P<.05), AT1a receptor mRNA was unchanged, and AT2 mRNA was increased (P<.05). PD123319 did not significantly modify any of these parameters. In conclusion, in salt-restricted, nephrectomized rats, selective antagonism of AT1-subtype receptors stimulates the expression and the activity of renin in the adrenal cortex. This observation demonstrates that Ang II locally formed in the adrenal cortex exerts a modulatory negative-feedback action on adrenal renin biosynthesis independent of the influence of the circulating renin-Ang system; this action is largely mediated through the AT1b-subtype receptors.

Adrenal Cortex

Role of tissue renin in the regulation of aldosterone biosynthesis in the adrenal cortex of nephrectomized rats.

The aim of the study was to investigate whether the adrenal renin-angiotensin system plays an independent role in the regulation of mineralocorticoid biosynthesis in the adrenal gland and to explore the mechanisms of this action. Twelve-week-old male Sprague-Dawley rats were studied: 22 rats were maintained on a regular diet; 27 and 22 rats received a low salt diet with and without treatment, respectively, with the angiotensin II (Ang II) AT1-subtype receptor antagonist losartan (10 mg/kg per day). A fraction of each group of rats underwent bilateral nephrectomy (n = 12, 15, and 10, respectively) and was killed 48 hours later. In an additional group of 24 (12 intact and 12 nephrectomized) rats, the effects of the Ang II AT2-subtype receptor antagonist PD123319 were investigated. In intact rats, plasma renin activity (PRA) and adrenal renin activity and expression were progressively raised by salt restriction and losartan, whereas aldosterone synthase mRNA and plasma aldosterone (PA) levels were increased by salt restriction and reduced by losartan. Forty-eight hours after nephrectomy, PRA fell to undetectable levels; in contrast, adrenal renin expression, assessed by semiquantitative reverse-transcriptase polymerase chain reaction (using GAPDH as a standard for gene expression), showed an 18-fold increase and was further increased after salt restriction and losartan (all P < .05). Also, adrenal renin activity was raised after nephrectomy and further increased after salt restriction (P < .05) and losartan. Cytochrome P450 aldosterone synthase expression in the adrenal cortex was stimulated by nephrectomy alone and by nephrectomy combined with low salt intake (P < .05), with consequent increases in PA concentrations. In losartan-treated salt-restricted nephrectomized rats, cytochrome P450 aldosterone synthase expression (P < .05 versus nephrectomy alone and nephrectomy plus salt restriction) and PA concentrations were diminished (P < .05) in spite of the observed increases of adrenal renin expression. The AT2-receptor antagonism did not significantly affect PRA, adrenal renin, and aldosterone biosynthesis and production in either intact or nephrectomized salt-restricted rats. These results demonstrate that the adrenal renin-angiotensin system plays an independent role in the regulation of mineralocorticoid biosynthesis in vivo. This action is mediated primarily via the Ang II AT1-subtype receptors.

Adrenal Glands

Epidemiologic surveillance of visceral leishmaniasis in Sicily, Italy.

Visceral leishmaniasis (VL) is endemic in Sicily. Although it is a notifiable disease, there is evidence that the actual number of cases is higher than that reported. In 1987, a regional reference center for active surveillance of VL was established and it recorded a total of 284 cases through 1995, a mean of 31.5 cases/year and about four-fold more than previously reported. Of the 284 cases, 150 (53%) were children (< or = 14 years of age), and of the 134 adults, 39 (29%) were coinfected with human immunodeficiency virus (HIV). The commonest viscerotropic zymodeme of Leishmania infantum, MON 1, was identified in 40 (93%) of 43 HIV-negative and eight (57%) of 14 HIV-positive patients. Among 280 patients evaluated (i.e., all HIV-negative and 35 of 39 HIV-positive subjects), 254 (91%) were treated with meglumine antimoniate alone or in combination with other drugs; 23 (8%) received allopurinol or amphotericin B, either conventional or in liposomal form; and three terminally ill patients were not treated. Among the 245 HIV-negative patients, 236 (96%) were successfully cured, while nine (4%) (seven adults) died during the course of antimonial treatment. None of the 35 HIV-positive patients was definitively cured, although mortality was apparently associated with other opportunistic infections.

Adolescent

[Static functional study with magnetic resonance of anterior shoulder instability].

We studied the glenohumeral joint, in its different components, with cine MRI. Ten asymptomatic volunteers and 6 patients with recurrent shoulder instability were examined with T2-weighted GE MR sequences on the axial plane with the subjects' arms rotated in different positions. The sections corresponding to the subcoracoid space and bicipital groove were recorded in closed-loop video format for cine display. Normal morphological glenoid labrum changes were demonstrated in different degrees of humerus rotation. The subscapularis tendon and the capsule were redundant and infolded toward the joint on internal rotation in 4/6 patients. We found capsular detachment in 2 patients, humeral head subluxation in 3 and subcoracoid impingement in 2 patients. Cine MRI permitted the accurate study of the changes in the glenoid labrum, capsule and subscapularis tendon in all patients and it also showed narrowed coracohumeral distance (< 11 mm) on internal rotation.

Humans

p53 expression compared with other prognostic factors in OMS grade-I stage-Ta transitional cell carcinoma of the bladder.

OBJECTIVE: Recent studies have investigated the possibility that p53 protein and some macroscopic tumoral features, such as diameter and focality of the lesion, play a significant prognostic role in bladder cancer progression. A retrospective study was conducted on papillary grade-I stage-Ta transitional cell carcinoma (TCC) of the bladder. METHODS: p53 expression was evaluated using the immunohistochemical method. A group of 31 patients with papillary grade-I and stage-Ta TCC of the bladder with no recurrence or who recurred with no histological grading and staging variation in a 4-year mean follow-up period was compared with 28 grade-I and stage-Ta papillary TCC patients who underwent recurrences and a worsening in histological grading (grade II or grade III) or staging (T1) within the same period of time. The aim of this study was to investigate the hypothesis that altered patterns of expression of the protein products of the mutated p53 tumor-suppressor gene, when independently evaluated in comparison with other tumoral prognostic factors, are associated with tumor recurrence and progression in patients with Ta papillary grade-I TCC of the bladder. RESULTS: Our data show that when a p53 threshold of > 0% was considered, 53.6% of patients with tumor progression in the follow-up period were p53-positive compared with only 16.1% of the nonprogressing group (chi 2 = 6, p = 0.02). On the contrary, p53 failed to show any value in predicting progression when a 5% threshold was considered (chi 2 = 1.12, p = 0.92). The multifocality of the tumoral lesion and recurrent tumor was highly predictive of tumor progression for both variables (chi 2 = 5.16, p = 0.003, and chi 2 = 0.23, p = 0.006, respectively). Multivariate analysis revealed p53 nuclear overexpression (at a threshold of > 0%) to be a single valuable prognostic factor of progression (OR = 10.20, p = 0.009) and recurrence (OR = 54.19, p = 0.01). CONCLUSIONS: Our results lead to the conclusion that p53 immunohistochemical detection has no prognostic value in predicting tumoral relapse or progression of TaGI TCC of the bladder when a 5% positivity threshold is considered. On the contrary, when a p53 nuclear labelling of > 0% is considered as positive staining, this tumor marker becomes highly predictive of tumor recurrence and progression. These findings seem therefore to suggest the use of a slight p53 positivity (> 0%) as a valid tool in predicting the clinical behavior of TaGI bladder TCC. The prognostic impact of a multifocal lesion and a recurrent tumor as markers of progression is also confirmed by these results.

Aged

Protein and amino acid metabolism in splanchnic organs in metabolic acidosis.

Metabolic acidosis causes a cooperative participation of different organs such as the liver, kidney, and muscle in restoring acid-base balance. In splanchnic organs, metabolic acidosis has repercussions on several nitrogen metabolism pathways. The decrease in urea synthesis due to reduced activity of urea cycle enzymes, ammonia uptake and amino acid transport, and changes in glutamine metabolism support renal ammoniagenesis thus offering a response to rid the body of excess protons. While some of the mechanisms are adaptive others may be harmful for the body. Metabolic acidosis may have effects on splanchnic protein turnover. In severe acidosis, synthesis of secreted liver proteins may be reduced. Acidosis may also modulate the response of the liver to growth hormone (GH) for insulin-like growth factor-I synthesis, thus inducing a state of GH resistance. Splanchnic abnormalities in acidosis might contribute to the malnutrition observed in uremia.

Acidosis

[Doppler color US in the diagnosis and treatment of iatrogenic pseudoaneurysms].

Pulsatile masses occur increasingly as a complication of transfemoral or transaxillary percutaneous catheterization, as the number of catheterization procedures and their complexity has increased. These iatrogenic injuries may be represented by a pseudoaneurysm or by a periarterial hematoma with transmitted arterial pulsation: the 2 vascular injuries require prompt differentiation because pseudoaneurysms need treatment by means of US-guided compression or surgical repair. Nineteen patients (10 men and 9 women, aged 40-85 years, mean: 62 years) with a groin (no. = 17) or axillary (no. = 2) pulsatile mass following angiographic catheterization were prospectively examined with color Doppler sonography (US). A pseudoaneurysm was detected in 13 patients (12 femoral and one axillary injury), whereas the other 6 pulsatile masses were consistent with periarterial hematomas. US-guided compression was attempted in 13 pseudoaneurysms and the pulsatile mass was repaired in 11/13 cases (84.6%), including 10/12 femoral and 1/1 axillary lesions. All the vascular injuries successfully treated with US-guided therapy were repaired 1-4 days after the angiographic complication. On the other hand, two pseudoaneurysms unsuccessfully treated with US-guided compression were studied after 8 and 24 days, respectively, after the angiographic complication and subsequently submitted to surgical repair. The pseudoaneurysms size did not seem to affect the favorable outcome of the US-guided treatment. With the exception of the 2 surgical cases, the other 17 patients underwent clinical examination and color Doppler US one and 7 days after the US-guided compression of the pulsatile mass. Moreover, a 6-25 weeks clinical follow-up showed no late complications or recurrences in all the cases. In conclusion, color Doppler US is now the technique of choice to assess potential complications related to femoral or brachial artery catheterization.

Adult

Kidney, splanchnic, and leg protein turnover in humans. Insight from leucine and phenylalanine kinetics.

The rate of kidney protein turnover in humans is not known. To this aim, we have measured kidney protein synthesis and degradation in postabsorptive humans using the arterio-venous catheterization technique combined with 14C-leucine, 15N-leucine, and 3H-phenylalanine tracer infusions. These measurements were compared with those obtained across the splanchnic bed, the legs (approximately muscle) and in the whole body. In the kidneys, protein balance was negative, as the rate of leucine release from protein degradation (16.8 +/- 5.1 mumol/min.1.73 m2) was greater (P < 0.02) than its uptake into protein synthesis (11.6 +/- 5.1 mumol/min. 1.73 m2). Splanchnic net protein balance was approximately 0 since leucine from protein degradation (32.1 +/- 9.9 mumol/min. 1.73 m2) and leucine into protein synthesis (30.8 +/- 11.5 mumol/min. 1.73 m2) were not different. In the legs, degradation exceeded synthesis (27.4 +/- 6.6 vs. 20.3 +/- 6.5 mumol/min. 1.73 m2, P < 0.02). The kidneys extracted alpha-ketoisocaproic acid, accounting for approximately 70% of net splanchnic alpha-ketoisocaproic acid release. The contributions by the kidneys to whole-body leucine rate of appearance, utilization for protein synthesis, and oxidation were approximately 11%, approximately 10%, and approximately 26%, respectively; those by the splanchnic area approximately 22%, approximately 27%, and approximately 18%; those from estimated total skeletal muscle approximately 37%, approximately 34%, and approximately 48%. Estimated fractional protein synthetic rates were approximately 42%/d in the kidneys, approximately 12% in the splanchnic area, and approximately 1.5% in muscle. This study reports the first estimates of kidney protein synthesis and degradation in humans, also in comparison with those measured in the splanchnic area, the legs, and the whole-body.

Adult

Association and cosegregation of stroke with impaired endothelium-dependent vasorelaxation in stroke prone, spontaneously hypertensive rats.

While hypertension is a major risk factor for stroke, it is not its sole determinant. Despite similar blood pressures, spontaneously hypertensive rats (SHR) do not share the predisposition to cerebrovascular disease typical of stroke-prone spontaneously hypertensive rats (SHRSP). We investigated vascular function in male SHR and SHRSP as well as in SHRSP/SHR-F2 hybrid animals. Animals were maintained on the appropriate dietary regimen necessary for the manifestation of stroke. Among the hybrid animals, a group of stroke-prone and a group of stroke-resistant rats were selected. Blood pressure was similar in all groups. Endothelium-independent vascular reactivity tested on isolated rings of thoracic aorta and basilar artery after death showed similar contractile and dilatory responses to serotonin and nitroglycerin, respectively, in all groups. In contrast, endothelium-dependent relaxation, in response to acetylcholine or substance P, was markedly reduced in SHRSP compared with SHR. Similarly, reduced vasodilatory responses were present in aortae of F2 rats that had suffered a stroke when compared with SHR or F2 rats resistant to stroke. The observed association and cosegregation of stroke with significant and specific impairment of endothelium-dependent vasorelaxation among SHRSP and stroke-prone F2 hybrids, respectively, suggest a potential causal role of altered endothelium-dependent vascular relaxation in the pathogenesis of stroke.

Acetylcholine