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Biomedical subjects

H Thurston

Publications and source records attributed to H Thurston.

At least 19 recordsLinked to original sources

An outbreak of Escherichia coli O157 gastroenteritis in a care home for the elderly.

In the summer of 2001 an outbreak of Escherichia coli O157 gastroenteritis affected staff and residents of a care home for the elderly in the West Midlands, UK. E. coli O157 phage type 2 was isolated from faeces in eight patients and 12 staff members. Thirty-five staff and 40 residents met the case definition for clinical gastrointestinal infection. Serological testing identified a further 14 possible cases of infection amongst asymptomatic staff and residents. The outbreak was atypical, as the disease seemed to be milder than has been observed in past outbreaks in similar settings. The index case, a member of staff, developed bloody diarrhoea and haemolytic-uraemic syndrome (HUS), but only one resident developed bloody diarrhoea and required hospitalization. No deaths occurred, despite the high-risk nature of the affected population. The source of the outbreak could not be identified. The prolonged nature of the outbreak and observed lapses in infection control practices indicated that person-to-person spread was the likely route of transmission. This outbreak illustrates the importance of observing appropriate infection control measures in the institutions providing residential and nursing care to the elderly.

Aged↗

Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study.

BACKGROUND: Different blood pressure (BP)-lowering drugs could have different effects on central aortic pressures and thus cardiovascular outcome despite similar effects on brachial BP. The Conduit Artery Function Evaluation (CAFE) study, a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT), examined the impact of 2 different BP lowering-regimens (atenolol+/-thiazide-based versus amlodipine+/-perindopril-based therapy) on derived central aortic pressures and hemodynamics. METHODS AND RESULTS: The CAFE study recruited 2199 patients in 5 ASCOT centers. Radial artery applanation tonometry and pulse wave analysis were used to derive central aortic pressures and hemodynamic indexes on repeated visits for up to 4 years. Most patients received combination therapy throughout the study. Despite similar brachial systolic BPs between treatment groups (Delta0.7 mm Hg; 95% CI, -0.4 to 1.7; P=0.2), there were substantial reductions in central aortic pressures with the amlodipine regimen (central aortic systolic BP, Delta4.3 mm Hg; 95% CI, 3.3 to 5.4; P<0.0001; central aortic pulse pressure, Delta3.0 mm Hg; 95% CI, 2.1 to 3.9; P<0.0001). Cox proportional-hazards modeling showed that central pulse pressure was significantly associated with a post hoc-defined composite outcome of total cardiovascular events/procedures and development of renal impairment in the CAFE cohort (unadjusted, P<0.0001; adjusted for baseline variables, P<0.05). CONCLUSIONS: BP-lowering drugs can have substantially different effects on central aortic pressures and hemodynamics despite a similar impact on brachial BP. Moreover, central aortic pulse pressure may be a determinant of clinical outcomes, and differences in central aortic pressures may be a potential mechanism to explain the different clinical outcomes between the 2 BP treatment arms in ASCOT.

Age Distribution↗

Telomere length in small-for-gestational-age babies.

OBJECTIVE: Short telomeres are associated with adult cardiovascular disease. Our aim was to determine whether small-for-gestational-age (SGA) newborns have shortened telomeres compared with appropriately grown controls. DESIGN: Prospective cohort study. SETTING: Large tertiary referral unit in Trent, UK. POPULATION: Seventy-two women who delivered at 35-42 weeks of gestation were recruited; 34 delivered SGA babies (less than or equal to the third birthweight centile) and 38 had appropriately grown babies (greater than the tenth centile). METHODS: Maternal and cord blood samples were collected at delivery. A Southern blot of DNA from these samples was hybridised with a 32P-labelled telomeric probe and telomere length was measured. MAIN OUTCOME MEASURES: Mean maternal and newborn telomere length. RESULTS: Maternal and newborn telomere lengths were significantly correlated in both the SGA and the control groups (r2 = 0.25, P < 0.0001). Telomere lengths were similar in both maternal (control 8.41 +/- 0.9 kb versus SGA 8.29 +/- 1.0 kb, P = 0.57) and newborn (control 10.36 +/- 1.5 kb versus SGA 10.33 +/- 1.3 kb, P = 0.93) cohorts in the two groups. CONCLUSIONS: Intrauterine events associated with impaired fetal growth do not appear to be associated with increased telomere shortening.

Adult↗

Evidence against potassium as an endothelium-derived hyperpolarizing factor in rat mesenteric small arteries.

1. Endothelium-derived hyperpolarizing factor (EDHF) has recently been identified as potassium released from endothelial cells into the myo-endothelial space. The present study was designed to test this hypothesis. 2. In rat small mesenteric arteries, mounted in a wire myograph, relaxation to acetylcholine or potassium was not significantly changed following incubation with oxadiazolo-quinoxalin-1-one (ODQ, 4 microM) and indomethacin (10 microM, n = 9). 3. Maximal relaxations to acetylcholine occurred in all arteries, were maintained and were significantly greater (P < 0.01, n = 9) than the transient relaxations to potassium, which only occurred in 30-40% of vessels. 4. Removal of the vascular endothelium abolished relaxant responses both to potassium and acetylcholine (P < 0.005, n = 9). 5. Compared with responses in 5.5 mM potassium PSS, relaxation responses to added potassium in arteries maintained in 1.5 mM potassium PSS were more marked and were not dependent on the presence of an intact endothelium (n = 8). 6. Incubation with BaCl2 (50 microM) significantly inhibited the maximal relaxant response to potassium in the presence of an intact endothelium in 5.5 mM potassium PSS (P < 0.05, n = 4), but had no effect on relaxation of de-endothelialized preparations in 1.5 mM potassium PSS (n = 5). 7. Treatment with ouabain (0.1 mM) abolished the relaxant response to potassium in 1.5 mM potassium PSS (P < 0.001, n = 9), but only partly inhibited the maximal relaxant response to acetylcholine in 5.5 mM potassium PSS (P < 0.01, n = 5). 8. These data show that at physiological concentrations of potassium an intact endothelium is necessary for potassium-induced relaxation in rat mesenteric arteries. Furthermore, the response to potassium is clearly different to that from acetylcholine, indicating that potassium does not mimic EDHF released by acetylcholine in these arteries.

Acetylcholine↗

Altered small artery morphology and reactivity in critical limb ischaemia.

Although the pathophysiology of critical limb ischaemia is poorly understood, there is evidence that the condition of the small arteries may determine the outcome of revascularization procedures. This study was designed to investigate the effects of critical limb ischaemia on the structure and function of the small arteries in the leg. Small arteries (<500 microm) from proximal (non-ischaemic) and distal (ischaemic) sites were obtained from patients undergoing bypass surgery for critical limb ischaemia and mounted in a myograph. Reactivity and morphological measurements were carried out and compared with controls. Control vessels from the thigh and calf showed no difference in media to lumen ratio. However, a comparison of ischaemic and non-ischaemic vessels from the patients with critical limb ischaemia showed significant thinning of the ischaemic vessel wall. Contraction studies using noradrenaline and angiotensin II revealed a significant decrease in the response of ischaemic vessels compared with the non-ischaemic vessels from the same patient. Moreover, these differences in reactivity were still apparent after the responses were corrected for wall thickness. Endothelial function assessed using the endothelium-dependent agonists acetylcholine and bradykinin showed a significantly impaired relaxation response to acetylcholine but not to bradykinin in the ischaemic vessels, and acetylcholine-induced relaxation was not improved after incubation with indomethacin. There was no change in the response to the endothelium-independent cAMP-mediated vasodilator iloprost but a significant impairment to sodium nitroprusside which acts via cGMP. These results suggest that small arteries in critical limb ischaemia are altered in both structure and function, with vessel wall thinning and impaired responses to acetylcholine and sodium nitroprusside.

Acetylcholine↗

An automatic device for the assessment of cardiovascular autonomic function.

Autonomic neuropathy is a common complication of diabetes mellitus and is associated with significant morbidity and possibly an increase in mortality. Despite this, however, autonomic dysfunction is not usually sought in the routine assessment of diabetic patients. We report the development and testing of a small, portable and reliable device that allows the routine testing of cardiac autonomic function in the outpatient setting with minimal inconvenience to the patient. This should facilitate the accurate assessment both of patients with symptoms suggestive of autonomic dysfunction and of autonomic function in research.

Arrhythmias, Cardiac↗

Investigating the relaxation, following diazo-2 laser flash photolysis, of a skinned trabecular preparation from SHR hypertrophied left ventricle.

Rat models of cardiac hypertrophy are characterised by a shift in left ventricular myosin isoform from V1 (adult) to V3 (foetal), the latter being associated with a slowing of the acto-myosin ATPase rate. The aim of this study was to examine hypertrophy effects on relaxation by investigating a chemically skinned cardiac preparation from the SHR, where all the cellular membranes are rendered non-functional allowing the myofibrils to be studied in isolation. On comparison, following photolysis of the photolabile caged Ca2+ chelator diazo-2, it can be seen that the SHR fibres relax at a slower rate than their age-matched WKY counterparts. We suggest that, since the thin filament regulatory proteins seem not to be affected by cardiac hypertrophy in the rat, this result can be attributed to the shift in left ventricular myosin isoforms. The reduced relaxation rate in the SHR could be the result of a slowing of the dissociation of actin and myosin during the cross-bridge cycle. These results have previously been published in abstract form [1].

Actins↗

Evidence of defective cardiovascular regulation in insulin-dependent diabetic patients without clinical autonomic dysfunction.

(1) Autonomic dysfunction is a well recognised complication of diabetes mellitus and early detection may allow therapeutic manoeuvres to reduce the associated mortality and morbidity. We sought to identify early cardiovascular autonomic neuropathy using spectral analysis of heart rate and systolic blood pressure variability. (2) Thirty patients with Type 1 (insulin-dependent) diabetes mellitus (DM) and 30 matched control subjects were studied. In addition to standard tests of autonomic function, heart rate and systolic blood pressure variability were assessed using power spectral analysis. From the frequency domain analysis of systolic blood pressure and R-R interval, the overall gain of baroreflex mechanisms was assessed. (3) Standard tests of autonomic function were normal in both groups. Total spectral power of R-R interval was reduced in the Type 1 DM group for low-frequency (473 +/- 63 vs. 747 +/- 78 ms2, mean +/- S.E.M., P = 0.002) and high-frequency bands (125 +/- 13 vs. 459+/-90 ms2, P < 0.0001). Systolic blood pressure low-frequency power was increased in the diabetic group (9.3 +/- 1.2 vs. 6.6+/-0.7 mmHg2, P < 0.05). The low frequency/high frequency ratio for heart rate variability was significantly higher in the Type 1 DM patients (4.6+/-0.5 vs. 2.9+/-0.5, P = 0.002), implying a relative sympathetic predominance. When absolute powers were expressed in normalised units, these differences persisted. There were significant reductions in baroreceptor-cardiac reflex sensitivity in Type 1 DM patients compared to controls while supine (9.7+/-0.7 vs. 18.5 +/- 1.7 ms/mmHg, P < 0.0001) and standing (2.9+/-0.9 vs. 7.18+/-1.9 ms/mmHg, P < 0.001). (4) Spectral analysis of cardiovascular variability detects autonomic dysfunction more frequently in Type 1 DM patients than conventional tests, and is suggestive of an abnormality of parasympathetic function. The abnormality of baroreceptor-cardiac reflex sensitivity could be explained by this impairment of parasympathetic function and this may predispose to the development of hypertension and increase the risk of sudden cardiac death. Using spectral analysis methods may allow detection of early diabetic cardiac autonomic neuropathy and allow therapeutic intervention to slow the progression.

Adult↗

Is impaired baroreflex sensitivity a predictor or cause of sudden death in insulin-dependent diabetes mellitus?

Sudden death at night is known to occur in young patients with insulin-dependent (Type 1) diabetes mellitus (IDDM) but the aetiology is uncertain. A cardiac arrhythmia has been postulated, but there has been little evidence to support this. We present the case of a 31-year-old man with IDDM of 17 years duration, who died suddenly while asleep. Over preceding months, he had had strict glycaemic control (HbA1 8.9%), normal 24 h blood pressure (mean 131 +/- 2.1/76 +/- 2.2 mmHg), no evidence of microangiopathy or endothelial dysfunction and normal standard clinical tests of autonomic function. An electrocardiogram was similarly unremarkable, with a QTc interval of 0.414 s, and an echocardiogram had demonstrated normal left ventricular mass index (96.4 g m-2). However, there was no nocturnal dip in heart rate (daytime 74 +/- 2.7, and nocturnal 68 +/- 1.6 beats min-1), and he had grossly impaired baroreflex sensitivity during Phase 4 of the valsalva manoeuvre (0.5 ms mmHg-1), with power spectral analysis studies suggesting an abnormality of parasympathetic function. The coroner's autopsy demonstrated no structural abnormalities. We hypothesize that abnormal baroreflex sensitivity could either predict a risk of or account for some of the unexplained deaths in IDDM, in that relative overactivity of the sympathetic nervous system could cause ventricular arrhythmias.

Adult↗

Endothelial function in subcutaneous resistance arteries from elderly hypertensive and normotensive subjects.

1. Previous studies have indicated that younger hypertensive subjects may have abnormal endothelium-dependent relaxation, which could contribute to the elevated peripheral resistance seen in established hypertension. This study was designed to examine the functional behaviour of the endothelium of small arteries from elderly hypertensive and normotensive subjects. 2. Resistance arteries were obtained from gluteal biopsies taken under local anaesthesia in 28 subjects of mean age 70 (range 60-76) years, and studied in an isometric myograph. Eighteen subjects had untreated essential hypertension, and 10 were normotensive. 3. After measurement of the contractile response to noradrenaline, relaxation responses to a variety of endothelium-dependent (acetylcholine and bradykinin) and endothelium-independent (iloprost and sodium nitroprusside) mechanisms were assessed in vessels precontracted with noradrenaline. Endothelium-dependent responses were also studied after incubation with NG-nitro-L-arginine to inhibit nitric oxide synthase. 4. There were no significant differences in the contraction or relaxation responses between elderly subjects with or without high blood pressure. Inhibition of nitric oxide synthase prevented any relaxation with acetylcholine and significantly attenuated the relaxation with bradykinin. Near-complete relaxation was however achieved with the endothelium-independent vasodilator sodium nitroprusside. 5. Hypertension in elderly subjects is not associated with a reduction in endothelial vasodilating function in the subcutaneous vessels of the gluteal region compared with age-matched normotensive controls. The results of this study do not support the hypothesis of a defect of resistance artery endothelium-dependent relaxation in the pathophysiology of hypertension in the elderly.

Acetylcholine↗

Can abnormalities of ventricular repolarisation identify insulin dependent diabetic patients at risk of sudden cardiac death?

OBJECTIVE: To study the possible association or QT dispersion and mean QTc intervals, as measured from standard 12 lead electrocardiograms, with baroreceptor-cardiac reflex sensitivity (BRS) in insulin dependent diabetic patients. DESIGN: Comparative study of non-invasive assessment of BRS, QT interval, and QT dispersion. SETTING: Large teaching hospital. SUBJECTS: 31 young asymptomatic, normotensive, insulin dependent diabetic patients, aged 20-55 years with normal clinical autonomic function. METHODS: QT intervals and QT dispersion were measured by a single observer blinded to other data about the patients. BRS was measured after activating the baroreflex with a Valsalva manoeuvre, and the rate in change of R-R interval to increasing systolic pressure during phase 4 was measured; in addition sequence analysis of resting systolic blood pressure and heart rate was performed during standing. The alpha coefficient--an index of the overall gain of the baroreflex mechanisms--was estimated from spectral analysis data of systolic blood pressure and pulse interval variability. RESULTS: Mean (SD) QTc interval was 406 (23) ms, QT dispersion was 44 (13) ms. There was no association between QT dispersion and any measurement of BRS. There was a negative correlation between mean QTc intervals and sequence analysis BRS (r = -0.355, P = 0.049), but no association with Valsalva BRS. The alpha coefficient, showed a significant negative correlation with mean QTc (r = -0.42, P = 0.008). CONCLUSIONS: Abnormal BRS may be reflected in the heart by global prolongation of ventricular repolarisation, but not by dispersion of ventricular repolarisation. This may, in part, explain the increase in sudden cardiac death seen in IDDM patients.

Adult↗

Assessment of baroreceptor-cardiac reflex sensitivity using time domain analysis in patients with IDDM and the relation to left ventricular mass index.

Autonomic dysfunction in insulin-dependent diabetic (IDDM) patients has been associated with abnormalities of left ventricular function and an increased risk of sudden death. A group of 30 patients with IDDM and 30 age, sex and blood pressure matched control subjects underwent traditional tests of autonomic function. In addition, baroreceptor-cardiac reflex sensitivity (BRS) was assessed using time domain (sequence) analysis of systolic blood pressure and pulse interval data recorded non-invasively using the Finapres beat-to-beat blood pressure recording system. 'Up BRS' sequences-increases in systolic blood pressure associated with lengthening of R-R interval, and 'down BRS' sequences-decreases in systolic blood pressure associated with shortening of R-R interval were identified and BRS calculated from the regression of systolic blood pressure on R-R interval for all sequences. We also assessed heart rate variability using power spectral analysis and, after expressing components of the spectrum in normalised units, assessed sympathovagal balance from the ratio of low to high frequency powers. IDDM subjects underwent 2-D echocardiography to assess left ventricular mass index. Standard tests of autonomic function revealed no differences between IDDM patients and control subjects, but dramatic reductions in baroreceptor-cardiac reflex sensitivity were detected in IDDM patients. 'Up BRS' when supine was 11.2 +/- 1.5 ms/mmHg (mean +/- SEM) compared with 20.4 +/- 1.95 in control subjects (p < 0.003) and when standing was 4.1 +/- 1.9 vs 7.6 +/- 2.7 ms/mmHg (p < 0.001). Down BRS when supine was 11.5 +/- 1.2 vs 22 +/- 2.6 (p < 0.001) and standing was 4.4 +/- 1.9 vs 7.3 +/- 2.5 ms/mmHg (p < 0.003). There were significant relations between impairment of the baroreflex and duration of diabetes (p < 0.001) and poor glycaemic control (p < 0.001). From a fast Fourier transformation of supine heart rate data and using a band width of 0.05-0.15 Hz as low-frequency and 0.2-0.35 Hz as high frequency total spectral power of R-R interval variability was significantly reduced in the IDDM group for both low-frequency (473 +/- 62.8 vs 746.6 +/- 77.6 ms2 p = 0.002) and high frequency bands 125.2 +/- 12.9 vs 459.3 +/- 89.8 ms2 p < 0.0001. When the absolute powers were expressed in normalised units the ratio of low frequency to high frequency power (a measure of sympathovagal balance) was significantly increased in the IDDM group (2.9 +/- 0.53 vs 4.6 +/- 0.55, p < 0.002 supine: 3.8 +/- 0.49 vs 6.6 +/- 0.55, p < 0.001 standing). Thus, time domain analysis of baroreceptor-cardiac reflex sensitivity detects autonomic dysfunction more frequently in IDDM patients than conventional tests. Impaired BRS is associated with an increased left ventricular mass index and this abnormality may have a role in the increased incidence of sudden death seen in young IDDM patients.

Adult↗

Randomized comparison of ultrasonic aspiration versus conventional electrocautery for dissection of the human internal thoracic artery.

The most common technique currently employed to harvest the internal thoracic artery for coronary artery bypass grafting is conventional electrocautery. This study compared an alternative method, electrocautery with an ultrasonic aspirator, for harvesting the internal thoracic artery. Patients were randomly assigned to one of six experimental groups (conventional electrocautery, ultrasonic aspirator at settings of 60%, 80%, and 100% power output, and ultrasonic aspirator in 100% CAVI-Pulse modes 1 and 3). Ring segments of internal thoracic artery were studied in an organ bath. Contraction responses were elicited with 123 mmol/L potassium physiologic salt solution, KPSS, KPSS solution containing noradrenaline, and a cumulative noradrenaline dose-contraction curve. Relaxation studies were performed with the vasodilators acetylcholine, bradykinin, and sodium nitroprusside. Forty percent of the electrocauterized vessels were traumatized or damaged and failed to respond to contractile stimuli, whereas only 10% of the vessels in ultrasonic aspirator groups 60%, 80%, and 100% failed to respond. All vessels in the group harvested by ultrasonic aspirator in 100% CAVI-Pulse mode 1 responded, whereas 20% of the vessels in the group harvested by ultrasonic aspirator in 100% CAVI-Pulse mode 3 failed to respond. All settings of electrocautery with an ultrasonic aspirator produced a greater contractile response to KPSS and noradrenaline. Acetylcholine and sodium nitroprusside produced similar relaxations in all groups, but the bradykinin responses were significantly improved in all groups undergoing 100% electrocautery with an ultrasonic aspirator. These results suggest that 100% electrocautery with an ultrasonic aspirator, particularly in 100% CAVI-Pulse mode 1, resulted in less damage and trauma than conventional electrocautery during harvesting of the internal thoracic artery.

Adult↗

Effect of angiotensin-converting enzyme inhibitors on resistance artery structure and endothelium-dependent relaxation in two-kidney, one-clip Goldblatt hypertensive and sham-operated rats.

1. This study was designed to examine the effect of angiotensin-converting enzyme inhibitors on resistance artery structure and endothelium-dependent relaxation in Goldblatt two-kidney, one-clip hypertensive rats. Four weeks after clipping, hypertensive and sham rats were treated with either perindopril (1 mg day-1 kg-1) or quinapril (3 or 30 mg day-1 kg-1). After 6 weeks mesenteric resistance arteries were mounted in a myograph for measurements of vascular structure. The endothelium-dependent relaxation response to acetylcholine and bradykinin and the response to the nitric oxide donor sodium nitroprusside were recorded. 2. All treatment regimes lowered the blood pressure and reversed both cardiac and resistance artery hypertrophy. Two-kidney, one-clip rats treated with quinapril showed a dose-dependent reduction in media cross-sectional area and media to lumen ratio. 3. Hypertension of 10 weeks' duration was associated with an impaired endothelium-dependent relaxation response to acetylcholine and bradykinin. Treatment with perindopril and either dose of quinapril prevented the development of impaired endothelium-dependent relaxation but had no effect on the response to sodium nitroprusside. Treatment had no effect on endothelium-dependent relaxation in sham rats. 4. Angiotensin-converting enzyme inhibitor treatment is effective in normalizing blood pressure and cardiovascular structural changes. Angiotensin-converting enzyme inhibitor treatment prevented the development of impaired endothelium-dependent relaxation to both acetylcholine and bradykinin. The ability of angiotensin-converting enzyme inhibitors to reverse cardiovascular structural changes and prevent the development of abnormal endothelium-dependent relaxation may contribute to the overall effect of this type of antihypertensive drug.

Acetylcholine↗

Abnormal baroreceptor-cardiac reflex sensitivity is not detected by conventional tests of autonomic function in patients with insulin-dependent diabetes mellitus.

1. Autonomic neuropathy is a common complication of diabetes mellitus and is a major risk factor for sudden death. 2. A group of 30 patients with insulin-dependent diabetes mellitus and 30 age-, sex- and blood pressure-matched control subjects underwent traditional tests of autonomic function. Resting supine R-R interval and systolic blood pressure variability were assessed using spectral analysis methods. In addition, we assessed the baroreceptor-cardiac reflex from the linear relation of the change in R-R interval to the increasing systolic blood pressure measured non-invasively with the Finapres monitor during phase 4 of the Valsalva manoeuvre and from resting heart rate and systolic blood pressure power spectra. 3. Whereas standard tests of autonomic function revealed no differences between patients with insulin-dependent diabetes mellitus and control subjects, there was a significant reduction in power spectral density of heart rate variability around the high-frequency region (125.2 +/- 112.9 versus 459.3 +/- 189.8 ms2, mean +/- SD). Furthermore, reductions in baroreflex sensitivity calculated from the Valsalva manoeuvre were detected in diabetics compared with controls (3.3 +/- 1.6 versus 9.5 +/- 2.5 ms/mmHg, mean +/- SD, P < 0.00001). There were significant relations between impairment of the baroreflex and duration of diabetes (P < 0.001) and poor diabetic control (P < 0.05). 4. In summary, autonomic dysfunction occurs much more frequently in diabetic patients than conventional tests would suggest. Abnormal baroreceptor-cardiac reflex sensitivity in patients with insulin-dependent diabetes mellitus may in part be explained by abnormal parasympathetic function. This unrecognized abnormality may have a role in the increased incidence of sudden death seen in young diabetic subjects.

Adult↗

Endothelium-dependent relaxation in resistance arteries from spontaneously hypertensive rats: effect of long-term treatment with perindopril, quinapril, hydralazine or amlodipine.

OBJECTIVE: To examine the effects of different types of antihypertensive treatment on endothelium-dependent relaxation in resistance arteries from spontaneously hypertensive rats (SHRs). DESIGN AND METHODS: Three-week-old SHRs were treated with the angiotensin converting enzyme (ACE) inhibitor perindopril (1 mg/kg/day) or quinapril (3 mg/kg/day) or the vasodilator hydralazine (50 mg/kg/day) or the calcium antagonist amlodipine (10 mg/kg/day). Control SHRs and Wistar-Kyoto (WKY) rats were treated with water. After 21 weeks rats were culled and mesenteric resistance arteries were mounted in a myograph. Relaxation responses to the endothelium-dependent vasodilators acetylcholine (ACh) and bradykinin were recorded before and after incubation with the nitric oxide synthase inhibitor NG-nitro-L-arginine (L-NOARG), as was the relaxation response to the nitric oxide donor sodium nitroprusside (SNP). RESULTS: All drugs prevented the rise in blood pressure found in the untreated SHRs. ACh-induced relaxation was significantly impaired in the untreated SHRs compared with the WKY rats. Treatment with either ACE inhibitor prevented the development of this impaired response. ACE inhibitor treatment significantly increased the relaxation response to bradykinin. Despite lowering blood pressure, hydralazine or amlodipine had no effect on ACh- or bradykinin-induced relaxation. Responses to SNP were not different between untreated SHRs and WKY rats and were not affected by drug treatment. CONCLUSION: Specific properties of certain antihypertensive drugs may play an important role in restoring endothelium-dependent relaxation in the small arteries that regulate peripheral resistance in the SHR.

Acetylcholine↗