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Biomedical subjects

M Castellano

Publications and source records attributed to M Castellano.

At least 73 records · Page 4Linked to original sources
PubMed1996

Vascular hypertrophy and remodeling in secondary hypertension.

It has been proposed that several neurohumoral factors may be involved in the genesis of vascular structural changes (remodeling or hypertrophy) frequently observed in essential hypertension. Therefore, in this study we investigated vascular structural alterations of subcutaneous small resistance arteries in patients with secondary forms of hypertension. The study included 70 participants: 11 with pheochromocytoma, 13 with primary aldosteronism, and 17 with renovascular hypertension; 13 normotensive subjects and 16 patients with essential hypertension served as controls. All subjects were submitted to a biopsy of subcutaneous fat. Small resistance arteries were dissected and mounted on a micromyograph, and media-lumen ratio, media thickness, remodeling index, and growth index were evaluated. Endothelial function was evaluated according to the dose-response curve to acetylcholine. In patients with either primary aldosteronism or renovascular hypertension, a marked increase in media-lumen ratio was observed, whereas in patients with pheochromocytoma, the extent of vascular structural alterations was similar to that observed in patients with essential hypertension. The increase in media-lumen ratio in patients with essential hypertension and with pheochromocytoma was mainly due to vascular remodeling (remodeling index, 93% to 94%), whereas in patients with renovascular hypertension, there was vascular growth (remodeling index, 70%; growth index, 53%). Patients with primary aldosteronism had an intermediate pattern compared with the other two forms of secondary hypertension. An evident impairment of endothelial function was observed in all four hypertensive groups. In conclusion, the renin-angiotensin-aldosterone system seems to be more powerful than the adrenergic system in inducing vascular growth.

Acetylcholine↗
PubMed1996

Angiotensin II type 1 receptor A/C1166 polymorphism. Relationships with blood pressure and cardiovascular structure.

The angiotensin II type 1 (AT1) receptor has a key role in mediating the vasoconstrictor and growth-promoting effects of angiotensin II. It has been reported that a polymorphism of the AT1 receptor gene (an A/C transversion at position 1166) may be associated with cardiovascular phenotypes, such as arterial blood pressure and aortic stiffness, that underlie a condition of increased cardiovascular risk. We examined a sample of 212 subjects randomly selected from a general population in northern Italy to investigate the role of AT1 receptor gene polymorphism, in the regulation of blood pressure and cardiovascular growth. We measured blood pressure (both clinic and 24-hour ambulatory recording), left ventricular mass (echocardiography), and carotid artery wall thickness (B-mode ultrasound); we assessed the AT1 receptor genotype by polymerase chain reaction and allele-specific oligonucleotide hybridization. Blood pressure values were lower in CC homozygotes than in heterozygotes and AA homozygotes; the difference was statistically significant for clinic measurements (mean difference for mean blood pressure, -6.6 mm Hg, P = .01; 95% confidence interval, -1.6 to -11.7 mm Hg) but not for ambulatory blood pressure measurements. CC homozygotes also presented a lower incidence of a positive family history of hypertension (P = .027). No statistically significant differences among AT1 receptor A/C1166 genotypes were observed for left ventricular mass or carotid artery wall thickness. We conclude that the present study does not support a major role of the AT1 receptor gene A/C1166 polymorphism as a marker of conditions associated with increased cardiovascular risk.

Blood Pressure↗
PubMed1996

[Coronary risk stratification and aspects of decision making after infarction].

The prognosis of myocardial infarction has considerably and favourably changed over the last decades thanks to new procedures in the hospital and post-discharge management. The identification of high-risk patients exposed to recurrent coronary events allows more appropriate treatment of these subjects and significantly contributes to the observed improvement in the general prognosis. In this short review, we examine different procedures for prognostic assessment in myocardial infarction and discuss a strategy for a favourable cost/benefit ratio in their utilization.

Combined Modality Therapy↗
PubMed1996

Persistence of left ventricular hypertrophy is a stronger indicator of cardiovascular events than baseline left ventricular mass or systolic performance: 10 years of follow-up.

OBJECTIVE: Left ventricular hypertrophy (LVH) and depressed left ventricular performance have been shown to be associated to an adverse prognosis in hypertensive patients. It has not been established, however, whether, during chronic antihypertensive treatment, the increased cardiovascular risk is more strictly related to the presence of LVH or of a low left ventricular performance. DESIGN AND METHODS: A total of 215 patients with uncomplicated hypertension (129 males, 86 females; age range 18-70 years, mean +/- SD 45 +/- 11) underwent an echocardiographic evaluation of left ventricular anatomy and function. In 151 patients (87 males, 64 females; age range 18-70 years, mean 45 +/- 10.4) the echocardiogram was repeated on average 10 +/- 1 years after the initial study. The presence of LVH (left ventricular mass index > 134 g/m2 in males and 110 g/m2 in females) and the midwall left ventricular shortening/end-systolic stress relationship were prospectively analysed as predictors of cardiovascular non-fatal events (n = 23) in patients who were seen at follow-up. RESULTS: The incidence of non-fatal cardiovascular events was greater in patients with LVH (n = 17, P < 0.0001) and in those with a lower midwall performance (n = 14, P < 0.01) at baseline. At follow-up, the incidence of non-fatal cardiovascular events was significantly greater in patients without a reduction in the left ventricular mass index, after adjusting for traditional risk factors (relative risk 3.52 versus 1.38 in patients with persistence and regression of LVH, respectively; P < 0.01). The baseline midwall fractional shortening was lower in patients with both persistence or regression of LVH (analysis of variance, P < 0.0001) than in patients with a normal left ventricular mass index. In logistic analysis, the left ventricular mass index at follow-up and age were independent determinants of non-fatal cardiovascular events (P < 0.001); without the left ventricular mass index at follow-up, this analysis showed that age, systolic blood pressure at follow-up and baseline midwall fractional shortening were independent determinants of non-fatal cardiovascular events. CONCLUSIONS: Our results suggest that lack of regression of LVH is a stronger indicator of cardiovascular risk than a depressed baseline midwall left ventricular performance.

Adolescent↗
PubMed1995

Dose-dependent dissociation of ACE-inhibitor effects on blood pressure, cardiac hypertrophy, and beta-adrenergic signal transduction.

BACKGROUND: Dose-dependent effects of ACE inhibitors on blood pressure, cardiac hypertrophy, and beta-adrenergic signal transduction were examined in an animal model with beta-adrenergic desensitization, which has been identified in failing hearts and in hypertensive cardiac hypertrophy. It is unknown whether beneficial ACE-inhibitor effects are due to an unloading of the failing heart or a reduction of neuroendocrine activation with beta-adrenergic resensitization. METHODS AND RESULTS: Low-dose (LD, 1 mg/kg) and high-dose (HD, 25 mg/kg) fosinopril treatment was performed in spontaneously hypertensive rats (SHR) and control (WKY) rats. Myocardial norepinephrine concentrations, adenylyl cyclase activity, beta-adrenergic receptors (radioligand binding), Gs alpha (functional reconstitution), and Gi alpha (pertussis toxin labeling) were determined. Ventricular weights and blood pressures were measured. HD but not LD reduced blood pressure and left ventricular weights in SHR. Isoprenaline- and guanylylim-idodiphosphate-stimulated adenylyl cyclase activities as well as beta 1-adrenergic receptors were reduced in SHR. The catalyst and Gs alpha were unchanged, but Gi alpha and norepinephrine concentrations were increased. Both LD and HD treatments restored beta-adrenergic alteration. CONCLUSIONS: LD treatment with ACE inhibitors restored beta-adrenergic signal transduction defects independently of regression of cardiac hypertrophy. This could contribute to the effects of ACE inhibitors in patients, who are often treated with nonhypotensive doses.

Adenylyl Cyclases↗
PubMed1995

Angiotensin-converting enzyme I/D polymorphism and arterial wall thickness in a general population. The Vobarno Study.

BACKGROUND: It has been reported that the D allele of an insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene is associated with conditions of increased cardiovascular risk, including left ventricular hypertrophy. METHODS AND RESULTS: Considering that a genetically determined overactivity of the renin-angiotensin system may influence cardiac as well as vascular growth, we investigated possible relations between ACE I/D genotype and carotid artery wall thickness (B-mode ultrasound) in 199 subjects, 50 to 64 years old, sampled from the general population of Vobarno, a small town in northern Italy. ACE DD genotype was associated with significantly higher common carotid artery intima-media thickness (P = .003). The occurrence of carotid atherosclerotic plaques was similar in the different genotypes. There was no association of the ACE I/D genotype with blood pressure values (either casual of 24-hour ambulatory monitored). CONCLUSIONS: ACE DD genotype may be considered a risk factor for the development of common carotid intima-media thickening in our study population.

Alleles↗
PubMed1995

Arterial spontaneous rhythmic contractile activity in humans and rats: spectral analysis and regulatory mechanisms.

OBJECTIVE: Many experimental observations have demonstrated the presence of spontaneous cyclic vasomotor activity (CVA) in large and small arteries. This study aimed to evaluate the characteristics of spontaneous CVA in rat and human resistance arteries, and to investigate its possible interference with the evaluation of sympathetic activity by means of spectral analysis of blood pressure in vivo. DESIGN AND RESULTS: In study 1 we examined small mesenteric arteries of spontaneously hypertensive rats and Wistar-Kyoto rats, as well as small omental arteries of normotensive subjects and hypertensive patients (Mulvany and Halpern technique). CVA was enhanced by the agonists of nitric oxide release, and was abolished by the inhibitors of nitric oxide or cyclic GMP synthesis. A potassium channel, which is barium- and zinc-sensitive and tetraethylammonium-insensitive, seems to play a crucial role in the genesis of CVA. In rats and in humans the frequency of CVA fell exactly in the frequency band ('low frequencies') of power spectral analysis of blood pressure usually considered to be an 'index of sympathetic activity'. In study 2, a power spectral analysis of blood pressure variability before and after intra-arterial infusion of noradrenaline or acetylcholine was performed in 18 patients with mild-to-moderate hypertension. The absolute and normalized spectral power of the low-frequency systolic blood pressure peak increased remarkably after noradrenaline and acetylcholine infusion, while its central frequency shifted from 0.10 Hz to approximately 0.06 Hz, exactly the frequency of CVA observed in vitro. CONCLUSIONS: A potassium channel appears to be involved in the genesis of CVA. Also, CVA might contribute to the blood pressure variability independently of the autonomic nervous system activity, and thus probably plays a role in the genesis of the low-frequency peak in the rat and in humans.

Acetylcholine↗
PubMed1995

Association of change in left ventricular mass with prognosis during long-term antihypertensive treatment.

OBJECTIVE: The aim of the present study was to assess the prognostic value of changes in left ventricular hypertrophy in hypertensive patients with time. DESIGN: Two hundred and fifteen uncomplicated hypertensive patients underwent a high-quality baseline echocardiogram for left ventricular anatomy evaluation and in 151 of those patients the echocardiographic examination was repeated 10 +/- 1.4 years after the initial study. METHODS: Left ventricular mass index changes were evaluated, in relation to the incidence of non-fatal cardiovascular events, adjusted for traditional cardiovascular risk factors. RESULTS: According to the presence or absence of left ventricular hypertrophy (left ventricular mass index > 134 g/m2 in men and > 110 g/m2 in women) at baseline and at the end of follow-up study, patients were divided into four groups: with normal left ventricular mass at both examinations (n = 78), with regression of left ventricular hypertrophy (n = 32), with persistence of left ventricular hypertrophy (n = 34) and with hypertrophy development (n = 7). After adjustment for traditional cardiovascular risk factors, the cumulative incidence of non-fatal cardiovascular events was significantly higher in the group of patients without regression of left ventricular hypertrophy. Cox survival analysis showed the presence of left ventricular hypertrophy at the end of follow-up study to be the most important factor related to cardiovascular events. CONCLUSIONS: The present findings strongly indicate that the lack of decrease or the increase of left ventricular mass after antihypertensive treatment can be associated with a higher risk for cardiovascular events, which is significantly reduced and almost normalized by complete regression of left ventricular hypertrophy.

Adolescent↗
PubMed1995

Relationship between sympathetic nervous system activity, baroreflex and cardiovascular effects after acute nitric oxide synthesis inhibition in humans.

OBJECTIVE: To examine the cardiovascular effects of acute systemic nitric oxide synthesis inhibition in humans in relation to the possible involvement of changes in sympathetic nervous system activity or in the baroreceptor reflex. DESIGN: Placebo or NG-monomethyl-L-arginine (250 mg by intravenous infusion for 5 min) was administered to seven healthy male volunteers according to a random, double-blind sequence. METHODS: Blood pressure and heart rate were measured non-invasively using a Finapres device from 20 min before to 80 min after starting infusion; beat-to-beat variability of blood pressure, pulse interval and systolic blood pressure and pulse interval covariation were assessed by means of spectral and sequence analysis methods. Under basal conditions and 15 min and 60 min after infusion, we measured stroke volume and indices of cardiac systolic and diastolic function by echocardiography, forearm blood flow by strain-gauge venous occlusion plethysmography, and plasma catecholamine levels. RESULTS: Compared with placebo, administration of NG-monomethyl-L-arginine caused a transient increase in blood pressure and reduction in heart rate. Stroke volume and indices of cardiac function did not change significantly, whereas cardiac index and forearm blood flow were significantly reduced after 15 min. Spectral analysis of blood pressure and pulse interval showed a significant reduction of power spectral density in the low frequencies (0.03-0.15 Hz) that persisted 60 min after infusion. The plasma noradrenaline level was significantly reduced after 15 min. No change in baroreflex engagement or sensitivity was detected by the cross-spectral or the sequence method. CONCLUSIONS: Acute systemic nitric oxide synthesis inhibition transiently increases blood pressure and reduces heart rate and cardiac index. The acute hypertensive response to NG-monomethyl-L-arginine is dependent neither on sympathetic nervous system activity, which is probably reduced as a consequence of baroreceptor reflex activation, nor on baroreceptor reflex sensitivity, which is not impaired.

Adult↗
PubMed1995

Chronic ACE-inhibitor treatment and adrenergic mechanisms in spontaneously hypertensive rats.

We investigated the effects of chronic treatment with the angiotensin-converting enzyme (ACE) inhibitor fosinopril on cardiac and vascular noradrenergic neurotransmission as related to cardiovascular hypertrophy in spontaneously hypertensive rats (SHRs). SHRs were treated with fosinopril at "high dose" (SHR-HD, 25 mg/kg/day) or "low dose" (SHR-LD, 1 mg/kg/day) from the 6th to the 12th week of age, and compared to age-matched untreated SHRs (SHR-C) and Wistar-Kyoto controls (WKY). Blood pressure was significantly reduced in SHR-HD but not in SHR-LD when compared to SHR-C. The antihypertensive dose of fosinopril reduced both cardiac and vascular hypertrophy, whereas the low dose was effective only in reducing vascular hypertrophy. Several differences in presynaptic and postsynaptic cardiovascular noradrenergic neurotransmission were observed between SHR-C and WKY rats (increased cardiac norepinephrine concentration, down-regulation of cardiac beta-adrenoceptors, reduced alpha-adrenergic receptor-mediated vasoconstrictor response of small mesenteric arteries to exogenous norepinephrine). All these differences were abolished by ACE inhibitor treatment, both at antihypertensive or at subantihypertensive doses. The results of this study are consistent with the hypothesis that chronic ACE inhibition may exert an inhibitory modulation on the peripheral adrenergic transmission, which is not related to blood pressure reduction. This modulation does not appear to be a determinant in preventing the development of cardiac hypertrophy but may play a role in the regression of vascular structural alterations in spontaneously hypertensive rats.

Analysis of Variance↗
PubMed1995

Effects of low and high doses of fosinopril on the structure and function of resistance arteries.

It has been suggested that angiotensin-converting enzyme inhibitors may induce a significant regression of cardiovascular hypertrophy not only through blood pressure reduction but also as a possible consequence of growth factor inhibition. The aim of this study was to evaluate the effects of the angiotensin-converting enzyme inhibitor fosinopril, given either at a hypotensive high dose or a nonhypotensive low dose, on structural and functional alterations of mesenteric resistance arteries and on cardiac mass in spontaneously hypertensive rats (SHR) and control Wistar-Kyoto rats. Fosinopril was administered in the drinking water from 6 to 12 weeks of age. Rats were killed at 12 weeks, and the ratio of heart weight to body weight was measured. Mesenteric arterioles were dissected and mounted on a micromyograph (Mulvany's technique). Vascular morphology (media-lumen ratio, media thickness) and endothelial function (response to acetylcholine) were then assessed. During the 6 weeks of treatment, systolic pressure in SHR treated with high-dose fosinopril was significantly lower compared with that in untreated SHR, whereas no difference was observed with low-dose fosinopril. In SHR treated with both high-dose and low-dose fosinopril, a statistically significant reduction of vascular structural alterations, in terms of both media-lumen ratio and media thickness, was observed. The ratio of heart weight to body weight was reduced only in SHR treated with high-dose fosinopril. An improvement in the endothelium-dependent relaxation to acetylcholine was observed in SHR treated with high-dose fosinopril compared with untreated SHR, whereas in SHR treated with low-dose fosinopril no improvement in endothelial function was detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1995

Contribution of systemic blood pressure to myocardial remodeling in uremic rats.

Left ventricular hypertrophy with diffuse intermyocardiocytic fibrosis is a feature of uremia. The role of blood pressure and/or other cardiovascular uremic risk factors in cardiac remodeling is still uncertain. To determine the extent to which improvement of kidney function and the control of uremia-related risk factors are associated with a reduction of myocardial injury, we evaluated the effect of dietary protein restriction or the angiotensin-converting enzyme inhibitor lisinopril on cardiac structure in remnant kidney rats. One week after subtotal nephrectomy, Wistar rats were allocated to receive drinking water solution (group 1), 5 mg/kg per day lisinopril (group 2), or a low-protein diet (6%) (group 3) for 12 weeks. Group 2 and 3 showed a comparable efficacy in preventing the expected rise in creatininemia, urinary protein excretion, and glomerulosclerosis. However, hypertension development was prevented only in group 2. Groups 1 and 3 developed a significant (P < .01) increase in left ventricular weight (2.45 +/- 0.1 and 2.5 +/- 0.5 mg/g body wt, respectively) compared with group 2 (1.9 +/- 0.06 mg/g body wt). Cardiac hydroxyporline concentration was also lower in group 2 compared with group 1 (2.07 +/- 0.16 versus 2.73 +/- 0.17 mg/g left ventricular weight, P < .05) but not compared with group 3 (2.59 +/- 0.19 mg/g left ventricular weight). The effect of angiotensin-converting enzyme inhibition on left ventricular mass and intracardiac collagen content appeared to be dissociated from anemia, sympathetic activity, and hyperlipidemia. There was a close relationship between systolic pressure and left ventricular mass; however, no relationship between the degree of cardiac fibrosis and systolic pressure could be determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Media: lumen ratio in human small resistance arteries is related to forearm minimal vascular resistance.

BACKGROUND: For the evaluation in humans of structural alterations in resistance arteries, most studies have used an indirect index, the measurement of minimal vascular resistance (mean blood pressure divided by maximal postischaemic blood flow) in suitable vascular beds. A sensitive and specific micromyographic technique was recently made available for the study of human small resistance arteries. Whether a correlation really exists between results obtained with the two techniques has not yet been investigated. OBJECTIVE: To evaluate both forearm minimal vascular resistance and media:lumen ratio of omental or subcutaneous small arteries in normotensive subjects and hypertensive patients. DESIGN AND METHODS: Thirty-four individuals were included in the study (age range 35-74 years; 24 hypertensive, 10 normotensive). Twenty-five had elective abdominal surgery and nine hypertensive patients had a gluteal biopsy. Omental and subcutaneous small arteries were dissected and mounted on a wire micromyograph (Mulvany's technique), and media:lumen ratio and media thickness were measured. The dose-response curve to noradrenaline was constructed at cumulative concentrations from 3 x 10(-9) to 3 x 10(-5) mol/l. Venous occlusion plethysmography was used to measure blood flow in the forearm, and minimal vascular resistance was calculated from mean blood pressure and postischaemic maximal blood flow (13 min ischaemia plus exercise). RESULTS: A statistically significant correlation was found between media:lumen ratio and minimal vascular resistance (r = 0.74, P < 0.001) as well as between media:lumen ratio and systolic (r = 0.44, P < 0.01) and diastolic (r = 0.38, P < 0.05) blood pressures. Similar correlations were observed between media thickness and systolic and diastolic blood pressures. Small arteries from hypertensive patients had a significantly increased reactivity to noradrenaline (by analysis of variance) compared with those from normotensive subjects, in terms of wall tension but not of active media stress. CONCLUSIONS: The present study demonstrated that the media:lumen ratio of small resistance vessels is significantly related to forearm minimal vascular resistance, suggesting that direct and indirect evaluations of vascular morphology will give similar results.

Adult↗
PubMed1995

Effects of antihypertensive therapy with angiotensin converting enzyme inhibitors or calcium antagonists on spontaneous cyclic vasomotor activity in small resistance arteries of spontaneously hypertensive rats.

OBJECTIVE: Spontaneous cyclic vasomotor activity can occur in small resistance arteries in vitro after precontraction with a vasoconstrictor. Calcium and potassium channels and nitric oxide synthesis or release seem to be involved in the genesis of this vasomotor activity. We therefore investigated the effects of chronic antihypertensive therapy with calcium antagonists and angiotensin converting enzyme (ACE) inhibitors on the amplitude and frequency of cyclic vasomotor activity in vitro in spontaneously hypertensive rats (SHR). MATERIALS AND METHODS: SHR were treated with fosinopril at 25 mg/kg per day or lacidipine at 10 mg/kg per day or nitrendipine at 30 mg/kg per day, from the age of 4 to 12 weeks. Data were compared with those obtained in untreated SHR and Wistar-Kyoto (WKY) rats. Half the rats were killed at 13 weeks of age, and the remaining half were killed at 38 weeks of age. The mesenteric small resistance arteries were dissected, mounted on a micromyograph and then contracted submaximally with noradrenaline. Acetylcholine was then added to the organ bath. RESULTS: More than 50% of the vessels showed cyclic vasomotor activity. The frequency and amplitude of this activity were greater in SHR than WKY rats after noradrenaline and after acetylcholine. At 13 weeks of age (but not at 38 weeks of age), treatment with a calcium antagonist (either lacidipine or nitrendipine) significantly reduced the frequency and amplitude of the vasomotor activity, probably by interfering with calcium entry. No change was observed after fosinopril. CONCLUSIONS: Antihypertensive treatment with different drugs may affect cyclic vasomotor activity differently, probably by interfering with cellular mechanisms involved in its genesis. The effects of calcium antagonists on cyclic vasomotor activity are still present after short-term but not after long-term treatment withdrawal.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Absence of central nervous system pathology in severe combined immunodeficiency mice intraperitoneally injected with peripheral blood lymphocytes from multiple sclerosis patients.

In order to reproduce some of the pathological features of multiple sclerosis (MS) we transplanted peripheral blood lymphocytes (PBLs) from seven patients with MS into the peritoneal cavity of 28 severe combined immunodeficiency (MS-SCID) mice. Seven SCID mice were also transplanted with PBLs from two healthy subjects (hu-SCID). Animals were sacrificed between 2 and 8 weeks after transplantation (a.t.). Polymerase chain reaction (PCR) using primers able to amplify the HLA-DQ alpha region showed presence of human cells in neural tissues of MS-SCID mice. Immunocytochemical analysis revealed the scattered appearance of human lymphocytes (mostly CD45RO+ T cells) in the meningeal space and choroid plexuses of MS-SCID brains. However, human lymphocytes were similarly found in brains of hu-SCID mice. Both groups of mice never showed signs or symptoms of neurological impairment. Our results indicate that the simple transplantation of lymphocytes from MS patients into SCID mice is not likely to produce an MS-like pathology.

Animals↗
PubMed1994

Vascular structural and functional alterations before and after the development of hypertension in SHR.

The time-course of the development of vascular and cardiac hypertrophy, as well as of arterial dysfunction, in human and experimental hypertension is still unclear. Moreover, the interrelationships between structural and functional vascular alterations are presently under debate. The aim of this study was to assess the arteriolar wall thickness and left ventricular mass as well as the vascular response to norepinephrine and acetylcholine in spontaneously hypertensive rats (SHR), before and after the development of hypertension, as compared to age-matched normotensive Wistar-Kyoto rats (WKY). Seventeen SHR (4 to 12 weeks old) and 17 WKY were included in the study. Blood pressure was measured noninvasively. After killing the animals, relative left ventricular mass (RLVM) was calculated, and mesenteric arcades were dissected and mounted on a micromyograph. Functional and structural characteristics of the vessels were measured: media thickness (MT), media/lumen ratio (M/L), and wall tension in response to norepinephrine and acetylcholine. At 4 weeks of age, no difference in blood pressure and RLVM between SHR and WKY was detected, but MT and M/L of mesenteric small resistance arteries were significantly greater in SHR. An increased response to norepinephrine was observed in terms of wall tension, but not of active media stress at the two higher norepinephrine concentrations. No difference in the dose-response curve to acetylcholine between SHR and WKY was observed. At 8 and 12 weeks of age systolic blood pressure was significantly higher in SHR; RLVM, MT, and M/L were also higher at this stage.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗