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PubMed1999

Low dose indapamide plus perindopril combination effects on cardiovascular structure and function in genetic hypertension.

1. Although the fixed combination preparations of thiazide and angiotensin-converting enzyme inhibitor are gaining wide acceptance in clinical practice, data on the basic pharmacology of the combinations are relatively limited. The long-term structural and functional effects of a fixed low dose (0.24 + 0.76 mg/kg per day) combination of indapamide + perindopril (I + P,S5590) is spontaneously hypertensive rats (SHR) were examined in the present study. 2. Male SHR (10-12 weeks) were treated with I + P or vehicle for 8 weeks. The blood pressure and heart rate were monitored by weekly measurements. At the end of the treatment period, left ventricular, aortic and intramyocardial coronary arteriole structures were assessed. Contractile and relaxant properties of mesenteric arteries were determined by wire-myography. 3. Indapamide + perindopril combination caused a significant lowering of both systolic (P < 0.001) and diastolic (P < 0.001) blood pressures. Left ventricle plus septum:bodyweight ratio (P < 0.001), aortic medial cross-sectional area (P < 0.05) and media:lumen ratios (P < 0.005) were all significantly reduced by I + P treatment. In contrast, the effect of I + P on intramyocardial coronary vascular structure did not reach statistical significance. There was some improvement in endothelium-independent vasorelaxation of mesenteric vessels but contractile responses to noradrenaline and calcium were unaffected by treatment. 4. In summary, a low dose I + P combination treatment of SHR partly normalizes both systolic and diastolic blood pressures. Cardiac and larger vessel hypertrophy was reversed but intramyocardial coronary arteriole structure was not as readily regressed by the end of the study.

Animals↗
PubMed2002

Characterization of small arteries isolated from the human placental chorionic plate.

Despite the essential role of the placenta in pregnancy, the control of the blood flow within the fetoplacental circulation is poorly understood. A handful of myography studies have directly assessed the role of vasoactive agonists in fetoplacental vasculature contractility but have used a range of steady-state conditions. Our aim, therefore, was to determine the optimal vessel diameter and oxygen tension to assess vascular function in small arteries isolated from the chorionic plate of normal term placentae. Biopsies were obtained from term placentae from uncomplicated pregnancies. Small arteries were dissected from the chorionic plate, mounted onto a wire myograph in HCO3(-) -buffered physiological salt solution at 37 degrees C and equilibrated for 20 min. Two methods for normalization of the optimal length/diameter for contractility of chorionic plate small arteries were assessed. Both classical normalization (CN) and length-tension curve (LTC) methods produced similar data. These data were agonist-independent. Data for CN and LTC were unaffected but maximal force generation (for U46619) was decreased in reduced oxygen tensions. Using conditions for optimal tension production in chorionic plate small arteries the thromboxane-mimetic U46619 produced the greatest and most reproducible constrictive effect. Relaxations were only achieved with endothelial-independent agonists (sodium nitroprusside and papaverine).

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2003

Maternal dexamethasone increases endothelin-1 sensitivity and endothelin a receptor expression in ovine foetal placental arteries.

Despite National Institutes of Health recommendations to administer antenatal steroids as a single course to women threatening preterm delivery, repeated treatments are often given. We investigated effects of repeated dexamethasone (DM) administered to the ewe on small maternal and foetal placental arteries. We hypothesized that DM would increase responsiveness to endothelin-1 (ET-1) and norepinephrine (NE) and that foetal arteries would react differently to ET-1 and NE compared to maternal arteries. Ewes received three treatments beginning at 103, 110, and 117 days of gestation (dGA). Each treatment consisted of four IM injections of 2mg DM or saline at 12-h intervals. At 119 dGA, in vitro functional studies were performed using Mulvany wire myography and endothelin receptor (ETR) expression was quantified using real-time RTPCR and receptor ligand autoradiography. Foetal placental arteries demonstrated greater maximal contractility to ET-1 and lesser maximal contractility to NE compared to maternal arteries. DM increased the maximal contraction elicited by ET-1 and NE in foetal but not maternal placental arteries. DM also increased the abundance of type-A ETR but not type-B ETR mRNA in foetal but not maternal placental arteries. However, within the whole placentome, DM increased the abundance of type-B ETR and decreased type-A ETR mRNA, which was confirmed by similar changes in ETR binding specifically within the labyrinth region. In summary, repeated DM treatment results in agonist and vascular bed specific responses within the placenta.

Animals↗
PubMed2000

[The stiff-man syndrome with diabetes mellitus type 1 and autoimmune thyroiditis].

HISTORY AND ADMISSION FINDINGS: A 54-year-old woman with type 1 diabetes of about 2 years' duration developed painful cramps in the muscles of the abdominal wall, the back and the thighs. On admission physical examination confirmed markedly increased tone of the muscles of the trunk and those proximal to it. INVESTIGATIONS: Markedly increased amounts of anti-GAD (glutamic acid decarboxylase) antibodies were present in both serum and cerebrospinal fluid (CSF). Electroneurography and -myography revealed mild polyneuropathy but no other neurological abnormality. DIAGNOSIS, TREATMENT AND COURSE: Suspected stiff-man syndrome (SMS) was confirmed by the increased anti-GAD antibodies and the marked improvement on gradually increasing doses of clonazepam. The autoimmune syndrome affected several organ systems: central nervous system (SMS), pancreas (diabetes), thyroid (immuno-thyroiditis). Immunosuppressive treatment with azathioprine was begun. The patient remains in good general condition 22 months after the initial diagnosis, and there have been no new organ involvement. CONCLUSION: It is important to include SMS in the differential diagnosis, even though the symptoms are not those of the full-blown picture of this rare disease. Absence of muscle cramps and myoclonus but presence of depressive symptoms can easily result in misdiagnosis, preventing early initiation of effective symptomatic treatment.

Azathioprine↗
PubMed2002

Is cardiovascular remodeling in patients with essential hypertension related to more than high blood pressure? A LIFE substudy. Losartan Intervention For Endpoint-Reduction in Hypertension.

BACKGROUND: Blocking the renin-aldosterone-angiotensin II system has been hypothesized to induce blood pressure-dependent as well as blood pressure-independent regression of cardiovascular hypertrophy. However, the relative influence of elevated blood pressure (BP) and various neurohormonal factors on cardiovascular remodeling in hypertension is unclear. METHODS: In 43 untreated patients with hypertension with electrocardiographic left ventricular hypertrophy, we measured relative wall thickness and left ventricular mass index by echocardiography and by magnetic resonance imaging (n = 32), intima-media cross-sectional area, and distensibility of the common carotid arteries by ultrasound, media/lumen ratio of isolated subcutaneous resistance arteries by myography, and median 24-hour systolic BP (n = 40), serum insulin, and plasma levels of epinephrine, norepinephrine, renin, angiotensin II, aldosterone, and endothelin. RESULTS: In multiple regression analyses, left ventricular mass index by echocardiography (R2 = 0.14, P <.05) and by magnetic resonance imaging (R2 = 0.32, P =.001) were associated with 24-hour systolic BP, whereas relative wall thickness was associated with plasma epinephrine (R2 = 0.12, P <.05) and aldosterone (R2 = 0.10, P <.05). Intima-media cross-sectional area/height was associated with 24-hour systolic BP (beta = 0.40) and plasma epinephrine (beta = 0.43) (adjusted R2 = 0.32, P <.001), whereas carotid distensibility was associated with 24-hour systolic BP (beta = 0.40) and plasma angiotensin II (beta = -0.41) (adjusted R2 = 0.30, P <.001). Media/lumen ratio in subcutaneous resistance arteries was associated with plasma epinephrine (R2 = 0.22, P <.01). CONCLUSION: Apart from being associated with a high BP burden, cardiovascular remodeling was associated with high levels of circulating epinephrine, aldosterone, as well as angiotensin II, suggesting a beneficial effect above and beyond the effect of BP reduction when using antihypertensive agents blocking the receptors of these neurohormonal factors.

Aged↗
PubMed2001

Developmental changes in reactivity of small femoral arteries in the fetal and postnatal baboon.

OBJECTIVE: We evaluated in vitro responsiveness of small arteries (internal diameter, 300 microm) from the femoral vascular bed of normal fetal (0.75-1.0 gestation) and neonatal (43-46 days) baboons to investigate whether the transition from fetal to neonatal life was associated with functional alterations in vasoconstrictor and vasodilator responses. STUDY DESIGN: The maximum response and sensitivity to potassium and to the constrictor agonists norepinephrine and U46619 (a thromboxane mimetic) were studied by in vitro myography. Vasodilator responses to the endothelium-dependent dilators acetylcholine and bradykinin were also investigated. RESULTS: The maximum response to norepinephrine and U46619 and to potassium increased with gestational age, whereas the sensitivity to these vasoconstrictors was similar in all groups studied. In contrast, acetylcholine- and bradykinin-induced relaxation (median effective concentration and maximum response) did not change with age. CONCLUSION: Receptor-mediated responses to a catecholamine, a prostanoid, and 2 endotheliumdependent vasodilators are similar in the fetal and neonatal baboon. The increase in maximal constriction with development, which is probably associated with growth or maturation of vascular smooth muscle, is likely to be a functionally important aspect in the development of cardiovascular function.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2002

Endothelial dysfunction in uterine circulation in preeclampsia: can estrogens improve it?

OBJECTIVE: The purpose of this study was to evaluate whether a 3-hour incubation with 17beta-estradiol will enhance blood flow- and bradykinin-mediated dilatation and alter pressure-induced basal tone in myometrial resistance arteries from women with preeclampsia and to evaluate the role of nitric oxide in the responses that were observed. STUDY DESIGN: Blood flow- and bradykinin-mediated dilatation and responses to intraluminal pressure of 60 and 80 mm Hg were compared before and after 3 hours of incubation with 17beta-estradiol (10(-8) mol/L) in isolated myometrial arteries with the pressure myography technique. In separate experiments, the role of nitric oxide on 17beta-estradiol-induced responses was evaluated in the presence of the nitric oxide synthase inhibitor (10(-4) mol/L). Endothelial morphologic condition was evaluated by scanning electron microscopy. RESULTS: Incubation with 17beta-estradiol significantly improved blood flow-mediated dilatation compared with initial blood flow-mediated response in arteries from women with preeclampsia. This effect was nitric oxide mediated, because the nitric oxide synthase inhibitor abolished the response. Arteries from women with preeclampsia demonstrated impaired bradykinin-mediated dilatation compared with that obtained in arteries from normal pregnant women. The 17beta-estradiol had no effect on bradykinin-mediated dilatation in arteries from women with preeclampsia. The enhanced pressure-induced tone at 80 mm Hg compared with the tone that developed at 60 mm Hg in arteries from women with preeclampsia was reduced after incubation with 17beta-estradiol. This reduction was also nitric oxide mediated. Morphologic signs of endothelial dysfunction were evident in arteries from women with preeclampsia. CONCLUSION: The 17beta-estradiol improved impaired blood flow-mediated dilatation and reduced basal tone through a nitric oxide-mediated pathway in isolated myometrial arteries from women with preeclampsia.

Adult↗
PubMed2001

Conditional and targeted overexpression of vascular chymase causes hypertension in transgenic mice.

We cloned a rat vascular chymase (RVCH) from smooth muscle cells (SMCs) that converts angiotensin I to II and is up-regulated in SMC from spontaneously hypertensive vs. normotensive rats. To determine whether increased activity of RVCH is sufficient to cause hypertension, transgenic mice were generated with targeted conditional expression of RVCH to SMC, with the use of the tetracycline-controlled transactivator (tTA). We confirmed conditional expression of RVCH by mRNA, protein, and chymase activity in the absence, but not in the presence, of dietary doxycycline. The systolic blood pressure (mmHg), measured by carotid artery cannulation at 10-12 weeks of age, was higher in tTA+/RVCH+ mice than in nonbinary transgenic littermates (136 +/- 4 vs. 109 +/- 3) (P < 0.05), as were the diastolic and mean pressures. Hypertension was completely reversed by doxycycline, suggesting a causal link with chymase expression. Medial thickening of mesenteric arteries from tTA+/RVCH+ mice vs. littermates (0.82 +/- 0.1 vs. 0.42 +/- 0.02) (P < 0.05) was associated with increased SMC proliferation, as judged by positive immunoreactivity, with the use of an antibody to the proliferating cell nuclear antigen. These structural changes were prevented by doxycycline. Perfusion myography of mesenteric arteries from tTA+/RVCH+ mice also revealed increased vasoconstriction in response to phenylephrine and impaired metacholine-induced vasodilatation when compared with littermate controls or with the doxycyline-treated group. Our studies suggest that up-regulation of this vascular chymase is sufficient to cause a hypertensive arteriopathy, and that RVCH may be a candidate gene and a therapeutic target in patients with high blood pressure.

Animals↗
PubMed2005

Umbilical artery Doppler waveform indices from normal pregnant women are related to vasodilatation of placental chorionic plate small arteries.

Blood flow control within the fetoplacental circulation is poorly understood despite the essential role of the placenta in pregnancy. Our study compared an in vitro assessment of placental chorionic plate small artery function with in vivo measures of umbilical artery blood flow. Umbilical artery Doppler waveform analysis was performed on women (N=8) with uncomplicated pregnancies within 24 hours of delivery. Small arteries (n=25) were dissected from the placental chorionic plate from biopsies at term and studied using parallel wire myography. Chorionic plate arteries developed maintained constrictions to the thromboxane-mimetic U46619. Nitric oxide (NO) donation with the endothelial-independent agent sodium nitroprusside elicited significant relaxation compared to paired control vessels. This vasodilatation correlated significantly with both pulsatility and resistance indices measured in the umbilical artery. We conclude that Doppler indices in the umbilical artery are inversely proportional to the maximal relaxation achieved by chorionic plate small arteries in response to a NO donor.

Adolescent↗
PubMed2000

A possible link between endothelial dysfunction and insulin resistance in hypertension. A LIFE substudy. Losartan Intervention For Endpoint-Reduction in Hypertension.

BACKGROUND: We wanted to investigate whether insulin resistance and time to steady state during isoglycemic clamp were associated with endothelial dysfunction, peripheral vascular remodeling and forearm blood flow (FBF) in patients with longstanding hypertension. METHODS: In 43 unmedicated, hypertensive patients with electrocardiographic-defined left ventricular hypertrophy we performed a 2-h oral glucose tolerance test and a 3-h isoglycemic hyperinsulinemic clamp with measurements of circulating plasma epinephrine and FBF by plethysmography. Delayed steady state was assessed by measuring the increase in insulin sensitivity from the second to the third hour of clamping. We measured 24-h ambulatory blood pressure, minimal forearm vascular resistance (MFVR) by plethysmography, media:lumen ratio (MLR) and acetylcholine-induced relaxation (AIR) in isolated, subcutaneous resistance arteries by myography. RESULTS: Insulin sensitivity after 2 and 3 h of clamping was not related to maximal AIR, MLR, MFVR or FBF. The increase in insulin sensitivity in men was negatively correlated to maximal AIR (r = -0.36, p < 0.05), and was independently correlated to relative changes in FBF (beta = 0.46) and in circulating epinephrine (beta = 0.33; adj. R = 0.33, p < 0.001). CONCLUSIONS: Insulin sensitivity was not correlated to parameters of peripheral vascular remodeling, endothelial function or microvascular rarefaction in patients with longstanding hypertension and left ventricular hypertrophy. However, the action of insulin on peripheral glucose uptake was influenced by endothelial dysfunction (delayed transcapillary insulin transport) and by changes in and/or redistribution of blood flow suggesting a link between vascular function and insulin sensitivity.

Aged↗
PubMed2004

Vasoconstriction of small arteries isolated from the human placental chorionic plate in normal and compromised pregnancy.

Our aim was to compare placental chorionic plate small artery function in normal pregnancies and those complicated by preeclampsia and intrauterine growth restriction. In particular we wished to test the hypothesis that the constrictive potential of placental small arteries is modified in compromised pregnancy. Biopsies were obtained from term placentas from uncomplicated pregnancies and those affected by preeclampsia and intrauterine growth restriction. Small arteries from the chorionic plate were dissected free from surrounding tissue and studied using parallel wire myography. Placental small arteries developed maintained constrictions to arginine vasopressin and the thromboxane-mimetic U46619. Arterial maximal constriction was reduced in both preeclampsia and intrauterine growth restriction. This effect was agonist independent. In intrauterine growth restriction, placental small arteries showed decreased sensitivity to U46619 but not to arginine vasopressin. Human placental chorionic plate small artery vasoconstriction is significantly reduced in compromised pregnancy, a factor that may lead to altered blood flow within the fetoplacental circulation in these conditions.

Adult↗
PubMed2003

Electrical impedance of muscle during isometric contraction.

Non-invasive measurements of the 50 kHz impedance of the anterior forearm show that the resistance and reactance increase under voluntary isometric contraction of the finger flexor muscles. The relationship between impedance and force is nonlinear, dependent on the type of test, the history of prior exercise, and the health status of the subject. Nevertheless, useful dynamic response parameters betaR = deltaR/R0deltaF and betax = deltaX/X0deltaF can be defined, typically a few hundredths of a per cent per newton. Evidence is presented for the view that these effects reflect dominantly physiological as opposed to morphological changes in the muscle. In particular, (a) the impedance changes many milliseconds before the force is generated, (b) betaR and betaX change substantially during a series of repetitions of the same exercise, and (c) the impedance does not return to its original value following relaxation of the muscle. Supporting data are presented for six healthy men and women, with ages ranging from 19 to 70 years. A preliminary study of patients with various neuromuscular diseases was also performed, amongst whom marked quantitative and qualitative contrasts with the healthy group were found. Further research aimed at assessing the clinical potential of such measurements is discussed, as are studies to elucidate the underlying mechanisms for the impedance changes. We propose the name 'dynamic electrical impedance myography' for this new technique.

Aged↗
PubMed2006

Electrical impedance in bovine skeletal muscle as a model for the study of neuromuscular disease.

Electrical impedance myography (EIM) consists of a set of bioimpedance methods configured for neuromuscular disease assessment, in which high-frequency electrical current is applied to a limb and the consequent surface voltage pattern over a muscle is evaluated. Prior human work has shown that the EIM parameters of resistance, reactance and phase change in different neuromuscular disease states including neurogenic and myopathic conditions. These parameters are also sensitive to the angle at which current is applied and measured relative to muscle fiber direction, a characteristic known as anisotropy. In order to obtain insights into the impedance characteristics of mammalian skeletal muscle without the confounding effects of an overlying skin-fat layer, bone and irregular muscle shape, we performed EIM on three 'nearly ideal' round 16 cm diameter, 1 cm equal thickness pieces of bovine rectus abdominis muscle. Using a standardized tetrapolar electrode array with 50 kHz electrical current, we identified strong anisotropy in the measured reactance and phase, with weaker anisotropy identified for resistance. We also found that increasing amounts of muscle maceration, a rough model of myopathic or traumatic muscle fiber injury, reduced phase and muscle anisotropy when current was injected perpendicular to the muscle fibers. These findings support that EIM parameters, including muscle anisotropy, are likely to be sensitive to the pathological changes that occur in neuromuscular disease states.

Algorithms↗
PubMed2003

Release by hypoxia of a soluble vasoconstrictor from rabbit small pulmonary arteries.

BACKGROUND: Soluble pulmonary vasoconstrictors released in response to hypoxia have been reported in pig and rat preparations, but not in rabbit preparations. METHODS: We used myography to evaluate the contribution of a soluble factor to constriction in rabbit small pulmonary arteries (external diameter 300-475 microm) exposed to 45 min hypoxia (PO(2)=9 mm Hg). RESULTS: Hypoxia produced gradually intensifying constriction. Return to euoxia (PO(2)=145 mm Hg) for 30 min relaxed only approximately 30% of the constriction, whereas elution of the myograph bath yielded full relaxation. Reapplication of the eluent gradually restored the constriction to its pre-elution level over a 30-min period. CONCLUSIONS: In this closed system, a soluble factor contributes substantially to hypoxic pulmonary vasoconstriction.

Animals↗
PubMed2004

Myofibrillar myopathy: clinical, morphological and genetic studies in 63 patients.

The term myofibrillar myopathy (MFM) was proposed in 1996 as a non-committal term for a pathological pattern of myofibrillar dissolution associated with accumulation of myofibrillar degradation products and ectopic expression of multiple proteins that include desmin, alphaB-crystallin (alphaBC), dystrophin and congophilic amyloid material. Subsequent studies revealed dominant mutations in desmin and alphaBC in some MFM patients, and clinical differences between kinships. We here review the clinical, structural and genetic features of 63 unrelated patients diagnosed as having MFM at the Mayo Clinic between 1977 and 2003. The age of onset was 54 +/- 16 years (mean +/- SD). Weakness was both proximal and distal in 77% and proximal only in 13%. Cardiomyopathy was diagnosed in 16%. Electro myography revealed a myopathic pattern associated with abnormal electrical irritability; 13 patients had abnormal nerve conduction studies but four of these had long-standing diabetes. The abnormal muscle fibres are best identified in trichrome-stained sections as harbouring amorphous, granular or pleomorphic hyaline structures, and vacuoles containing membranous material. The hyaline structures are strongly congophilic. Semiquantitative analysis in each case indicates that among the abnormal fibres, an average of 90, 75, 75, 70 and 70% abnormally express myotilin, desmin, alphaBC, dystrophin and beta-amyloid precursor protein, respectively. Therefore, immunostains for these proteins, and especially for myotilin, are useful adjuncts in the diagnosis of MFM. Electron microscopy shows progressive myofibrillar degeneration commencing at the Z-disk, accumulation of degraded filamentous material and entrapment of dislocated membranous organelles in autophagic vacuoles. In all patients, we searched for mutations in desmin and alphaBC, as well as in telethonin, a Z-disk-associated protein, or in syncoilin, which together with plectin links desmin to the Z-disk. Two of the 63 patients carry truncation mutations in the C-terminal domain of alphaBC, four carry missense mutations in the head or tail region of desmin, and none carries a mutation in syncoilin or telethonin. Thus, MFM is morphologically distinct but genetically heterogeneous. Further advances in defining the molecular causes of MFM will probably come from linkage studies of informative kinships or from systematic search for mutations in proteins participating in the intricate network supporting the Z-disk.

Adolescent↗
PubMed1986

Excitation-contraction coupling in rat myocardium: alterations with long term ethanol consumption.

The mechanical and electrical effects of chronic ethanol consumption were studied in rats maintained on 40% ethanol and water solution (40% of caloric intake) for a 30 week period and in controls. Left ventricular papillary muscles from male Wistar rats were studied by myography at 30 degrees C, 0.1 Hz stimulation, and external calcium concentration of 2.4 mmol X litre-1. No significant difference was found between alcoholic and control rats with regard to resting tension. Developed tension, time to peak tension, time to one half relaxation, and time to peak shortening were, however, significantly decreased in preparations from the study animals. Velocity of shortening and relengthening at all relative loads studied were depressed in alcoholic preparations. No significant difference was found in action potential between the two groups with regard to resting membrane potential, action potential amplitude, overshoot, or maximum rate of rise of the upstroke. In contrast, the duration at 50% (APD50) and 75% (APD75) of total repolarisation was significantly shorter for action potential in the alcoholic group than in the controls. Thus chronic ethanol ingestion results in an inability to develop normal levels of force, depressed force-velocity relation, and shortening of action potential duration.

Action Potentials↗
PubMed2001

Neuromuscular monitoring.

This review summarizes recent reports on the techniques and the use of methods for monitoring neuromuscular function during anaesthesia. The latest news on the use of acceleromyography in the face and hand, on laryngeal and diaphragmal surface electromyography, on acoustic myography, on evaluation of intense neuromuscular block, and on postoperative residual curarization is presented and discussed. It is concluded that available evidence suggests that more attention should be paid by the anaesthetist to the problems of residual curarization and hence to proper monitoring of neuromuscular function using objective methods.

Journal Article↗
PubMed1999

Functional reduction and associated cellular rearrangement in SHRSP rat basilar arteries are affected by salt load and calcium antagonist treatment.

The stroke-prone spontaneously hypertensive rat (SHRSP) is a strain with high incidence of cerebrovascular accidents increased by salt-rich diet and decreased by calcium-antagonist treatment. In the SHRSP rat basilar artery the authors have previously shown reduced contractility and altered structure including regions of smooth muscle cell (SMC) disorganization. The aims of this study have been to analyze (1) the morphology of these abnormal regions, (2) the structural modifications responsible for the reduced function, and (3) the effect of salt and calcium-antagonist treatment on vascular structure and function. Wistar Kyoto and SHRSP rats, untreated or treated from week 8 through 14 with 1% NaCl or 1% NaCl + 1 mg x kg(-1) x d(-1) lacidipine, were used. Function was studied with wire myography. Structure was analyzed in fixed intact arteries with confocal microscopy. Basilar arteries from SHRSP rat showed (1) reduced contractility, (2) discrete foci of SMC disarray with altered proportion of adventitia to SMC, and (3) decreased SMC and increased adventitial cell number. Arteries from salt-loaded SHRSP rats showed a higher degree of SMC disarray and further reduction in contractility. Lacidipine treatment of salt-loaded rats significantly improved structure and function. These data suggest that vascular remodeling can provide an explanation for the observed reduction in vascular contractility of SHRSP rat basilar arteries and might show light on the effects of salt load and calcium-channel blockers in life span and the incidence of cerebrovascular accidents in SHRSP rats.

Animals↗