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Biomedical subjects

H Thurston

Publications and source records attributed to H Thurston.

At least 37 records · Page 2Linked to original sources
PubMed1996

The effect of insulin treatment and of islet transplantation on the resistance artery function in the STZ-induced diabetic rat.

1. This study was designed to investigate the influence of insulin treatment and islet transplantation on the smooth muscle contractility and endothelium-dependent and independent relaxation of resistance arteries in the chemically induced streptozotocin (STZ) diabetic rat after 6-8 weeks, and 12-14 weeks of diabetes, compared to non-diabetic age-matched controls. 2. The morphology, and contractile responses to high potassium physiological salt solution (KPSS), KPSS containing 10(-5) M noradrenaline (NAK), and concentration-response curves to noradrenaline (NA) of mesenteric resistance arteries were recorded, along with the endothelium-dependent relaxation responses to acetylcholine (ACh) and bradykinin (BK), and endothelium-independent relaxation to sodium nitroprusside (SNP). Concentration-response curves were then repeated in the presence of a nitric oxide synthase inhibitor, NG-nitro-L-arginine (L-NOARG). 3. Insulin-treated diabetic rats in the 12 week study demonstrated enhanced vascular contractility to KPSS, NAK and NA, compared to age-matched non-diabetic controls. 4. Incubation with L-NOARG resulted in both a significant increase in maximum contractile response, and sensitivity (pD2) to NA in the untreated diabetic group (6 weeks). A significant shift in sensitivity was also seen in the insulin-treated diabetic group. In the 12 week study, incubation with L-NOARG resulted in an increased maximum contractile response and sensitivity to NA in the insulin-treated diabetics. An increase in sensitivity was also observed in the untreated diabetic group. 5. Endothelium-dependent relaxation to ACh was significantly augmented in the untreated diabetics (6-weeks), compared to the control group. In the 12-week study, relaxation to both ACh and BK was not significantly different in any of the experimental groups when compared to the sham-operated non-diabetic controls. 6. Incubation with L-NOARG resulted in a significant attenuation of the maximum relaxation response to ACh and BK in all of the experimental groups, in the 6- and the 12-week study. 7. There was no significant difference in the maximum relaxation response or sensitivity to sodium nitroprusside between the diabetic groups and their age-matched controls in either the 6-week or the 12-week study. 8. The results of this study suggest an enhanced release of nitric oxide in the early stages of diabetes, which is more evident in the untreated diabetic rats than the insulin treated, and appears to normalize as the duration of diabetes progresses. This study also shows that the alteration in vascular reactivity of the resistance arteries can be restored to within normal limits by the transplantation of islets of Langerhans, and that islet transplantation is an effective strategy in the correction of the metabolic abnormalities associated with insulin-dependent diabetes.

Analysis of Variance↗
PubMed1996

Reproducibility of the circadian blood pressure fall at night in healthy young volunteers.

The aim of this study was to evaluate the reproducibility of the circadian blood pressure (BP) change in normal healthy volunteers. The subjects were 32 healthy, young, normotensive volunteers who underwent 24 h ambulatory BP monitoring on two occasions, at least 4 weeks apart. Data were analysed using standard definitions of day and night (i.e. 07.00-22.00 for daytime and 22.00-07.00 for night time), event diaries to identify individual's day and night time and a time independent method (cusum analysis). Intraindividual variations of BP were assessed using the coefficient of variation (CV). The mean 24 h BP was very reproducible with a CV of 4.7%. Using the fixed definition of day and night, mean night time systolic blood pressure (SBP) was significantly reduced on the second visit compared to the first (P < 0.001). Using fixed times for day and night, day-night difference was poorly reproducible, with a CV of 52% for SBP and 59% for diastolic blood pressure (DBP), however this improved using diary based day-night to 40/41% and cusum analysis to 24.6/28.1%. We recommend that circadian BP changes are studied using individual definitions of day and night or time independent methods such as cusum analysis.

Adult↗
PubMed1995

The effect of insulin on the vascular reactivity of isolated resistance arteries taken from healthy volunteers.

Impaired reactivity of the resistance vasculature may contribute to the development of diabetic microangiopathy by altering microvascular haemodynamics. This study investigates the acute effects of insulin on the contractility and relaxation properties of isolated human resistance arteries (< 300 microns internal diameter) taken from gluteal subcutaneous fat of 33 (18 male: 15 female) normotensive healthy volunteers (supine blood pressure 115.6 +/- 1.6/70.0 +/- 1.5 mm Hg [mean +/- SEM], with no family history of hypertension or diabetes mellitus. Resistance arteries were mounted in a small vessel myograph to measure isometric tension. Contractile responses to noradrenaline were reduced after incubation in 1 mU/ml of insulin for 20 min (p < 0.01; Group 1). Increasing concentrations of insulin were found to reduce the contractile response to noradrenaline in a dose-dependent manner (Group 2; 0.1 mU/ml by 8% [p < 0.01], 1 mU/ml by 17% [p < 0.02] and 10 mU/ml by 22% [p < 0.01]). Sensitivity to insulin (ED50) only decreased at the highest concentration of insulin. However, acetylcholine-induced relaxation was not altered by insulin (Group 2). Time control studies (Group 3) showed that contractile and relaxation responses over the 4-h study period were unchanged. Furthermore, the length of time the vessels were exposed to insulin did not progressively impair responses (Group 4). These findings suggest that insulin may induce abnormalities in vascular smooth muscle contractility, a factor that may contribute to or exacerbate the abnormal haemodynamics observed in the capillary microcirculation of numerous vascular beds in diabetes.

Acetylcholine↗
PubMed1995

Impaired endothelium-dependent relaxation in isolated resistance arteries of spontaneously diabetic rats.

1. Previous studies have shown that endothelium-dependent relaxation in the aorta of spontaneously diabetic bio bred rats (BB) is impaired. 2. We have investigated noradrenaline (NA) contractility, endothelium-dependent acetylcholine (ACh) and bradykinin (BK) relaxation, and endothelium-independent sodium nitroprusside (SNP) relaxation in mesenteric resistance arteries of recent onset BB rats and established insulin treated BB rats, compared to their age-matched non diabetic controls. 3. There was no significant difference in the maximum contractile response or sensitivity to noradrenaline in either of the diabetic groups compared to their age-matched controls. 4. Incubation with the nitric oxide synthetase inhibitor NG-nitro-L-arginine (L-NOARG) resulted in a significant increase in maximum contractile response to noradrenaline in the recent onset age-matched control group (P < 0.05). Analysis of the whole dose-response curve (using ANOVA for repeated measures with paired t test) showed a significant left-ward shift following the addition of L-NOARG (P < 0.001). A similar but less marked shift (P < 0.01) was evident in vessels from recent onset diabetics. An overall shift in both sensitivity and maximum response was also evident in the age-matched non diabetic controls of the insulin-treated group (P < 0.05). However, by contrast, there was no significant change in sensitivity in the insulin-treated diabetic rats. 5. ACh-induced endothelium-dependent relaxation was significantly impaired in the recent onset diabetic rats compared to their age-matched controls (47 +/- 11% versus 92 +/- 2%, P < 0.05, n = 6), and in the insulin treated diabetic rats (34 +/- 5% versus 75 +/- 6%, P < 0.05, n = 6). The relaxation responses to BK also were significantly impaired in the diabetic rats compared to their age-matched controls (recent onset: 20 +/- 3% versus 72 +/- 7%, P < 0.05, n = 6; insulin treated: 12 +/- 9% versus 68 +/- 7%, P < 0.05, n = 7). 6. Incubation with either the nitric oxide synthetase substrate, U-arginine, or the free radical scavenging enzyme superoxide dismutase (150 mu ml-1) failed to improve the attenuated response of acetylcholine-induced relaxation in the diabetic vessels. 7. Endothelium-dependent relaxation mediated by ACh and BK was significantly attenuated in both the diabetic and control vessels after incubation with L-NOARG. 8. Pretreatment with a cyclo-oxygenase inhibitor, indomethacin, significantly enhanced the relaxation to ACh in both the recent onset and insulin treated diabetic rats (42 +/- 10%, n = 7 versus 64 +/- 7%, n = 7, P < 0.05, and 40 +/- 5%, n = 7 versus 65 +/- 9%, n = 6, P < 0.05). 9. Following endothelium removal, there was a marked impairment in endothelium-dependent relaxation responses to ACh and BK in both the diabetic and control vessels. 10. Incubation with the thromboxane A2 receptor antagonist SQ29548, did not significantly improve the ACh endothelium-dependent relaxation response in the diabetic vessels. 11. Endothelium-independent relaxation to sodium nitroprusside was significantly impaired in the first group of diabetic vessels studied; however, subsequent studies showed no impairment of the sodium nitroprusside response in the diabetic vessels. 12. In conclusion, the ability of the endothelium to regulate vascular contractility is reduced in recent onset diabetic vessels, and significantly impaired in established insulin treated diabetics. Relaxation to the endothelium-dependent vasodilators ACh and BK was impaired in both the recent onset and the established insulin treated diabetics, and the ACh response was significantly improved following pretreatment with indomethacin, suggesting a role for a cyclo-oxygenase-derived vasoconstrictor. Preliminary studies with a thromboxane A2, receptor antagonist, SQ29548 did not significantly improve the impaired relaxation to ACh, indicating that the vasoconstrictor prostanoid is not thromboxane A2.

Acetylcholine↗
PubMed1995

Pulse pressure and resistance artery structure in the elderly.

There has been recent interest in the possibility that resistance vessel structural adaptation in hypertension may be more closely related to pulse pressure than to other blood pressure parameters. We investigated the relation between blood pressure and resistance vessel structure in a group of subjects from an age group (older than 60 years) in which a widening of pulse pressure is a typical finding and characterized blood pressure parameters using 24-hour ambulatory blood pressure monitoring. We studied resistance vessels retrieved from biopsies of skin and subcutaneous fat taken from the gluteal region of 32 subjects under local anesthesia (age, 70 +/- 1 years [mean +/- SEM], 21 of whom were hypertensive and 11 normotensive. Media-lumen ratio was higher in the hypertensive than the normotensive subjects (18.6 +/- 1.6% versus 12.8 +/- 1.2%, P < .01) and correlated with age (r = .44, P < .05), clinic systolic pressure (r = .35, P < .05), 24-hour systolic pressure (r = .40, P < .05), and 24-hour pulse pressure (r = .56, P < .001). Stepwise multivariate regression analysis identified clinic and 24-hour pulse pressure as the only significant predictors of media-lumen ratio independent of age, other parameters of clinic blood pressure, and blood pressure variability (R2 = 41%, P < .05). These findings confirm those from animal models of hypertension in demonstrating the importance of pulse pressure in relation to cardiovascular structural adaptation and have important implications for the goals of treatment of hypertension in the elderly.

Aged↗
PubMed1994

Impaired contraction and endothelium-dependent relaxation in isolated resistance vessels from patients with insulin-dependent diabetes mellitus.

1. An increase in capillary blood flow and pressure has been implicated in the pathogenesis of diabetic microangiopathy. Abnormal vascular reactivity of the resistance vasculature may play a contributory role by permitting alterations in regional haemodynamics. 2. We have studied the contractile behavior of isolated resistance arteries from normotensive patients with insulin-dependent diabetes mellitus and non-diabetic matched control subjects. Contractile responses to potassium (123 mmol/l), noradrenaline (10(-8) to 3 x 10(-5) mol/l) and angiotensin II (10(-11) to 3 x 10(-8) mol/l) were recorded. Relaxation studies were performed in maximally contracted vessels using acetylcholine (10(-8) to 10(-5) mol/l) and bradykinin (10(-9) to 10(-6) mol/l) (endothelium-dependent) and sodium nitroprusside (10(-9) to 10(-5) mol/l) (endothelium-independent). 3. The maximal contractile responses to potassium (P < 0.05), noradrenaline (P < 0.01) and angiotensin II (P < 0.01) were depressed in diabetic patients. Relaxation to acetylcholine was impaired (P < 0.05), but was normal with bradykinin and sodium nitroprusside. 4. These results suggest that there may be a defect in the endothelial cell acetylcholine receptor excitation-coupling in diabetes mellitus rather than a decreased ability to synthesize and release endothelium-derived relaxing factor. Impaired contraction and endothelium-dependent relaxation of resistance arteries in diabetic patients may contribute to the development of diabetic microangiopathy by causing an increase in tissue blood flow, a rise in capillary pressure and, as a result, an increase in vascular permeability.

Acetylcholine↗
PubMed1994

Heterogeneity of vascular DNA synthesis in response to the development of Goldblatt two-kidney, one clip hypertension.

OBJECTIVE: To examine the changes in the rate of DNA synthesis in the aorta and mesenteric and subcutaneous resistance arteries during the development of renovascular hypertension. METHODS: Goldblatt two-kidney, one clip hypertensive and sham-operated control rats were studied 3, 7, 14 and 28 days after surgery. DNA synthesis was measured as the hourly rate of [3H]-thymidine incorporation into the DNA. RESULTS: Three days after renal artery constriction there was a significant increase in the DNA synthesis in both the aorta and the mesenteric vessels, although the blood pressure was not changed. DNA synthesis was elevated during the development of hypertension, but returned to control levels after 28 days when the blood pressure had reached a plateau. By contrast, there was no increase of DNA synthesis in the subcutaneous vessels at any time after renal artery constriction. The plasma renin concentration also was increased after 3 days in the clipped rats and remained elevated throughout the study. There were no significant changes in the blood pressure, the plasma renin concentration or the rate of vascular DNA synthesis in the sham-operated control rats. CONCLUSIONS: These data indicate that there are regional differences in the vascular response to the induction of renovascular hypertension and that in some vascular beds an increase in DNA synthesis precedes the rise in blood pressure.

Animals↗
PubMed1993

The effects of intraoperative vasodilators and angiographic contrast medium on the endothelium and smooth muscle cells of vein grafts.

Cellular injury is a major cause of intimal hyperplasia in vein grafts. The effects of exposure of vein samples to iopamidol, papaverine and iloprost were studied in vitro in an organ chamber to determine whether these agents cause endothelial and/or smooth muscle cell injury. Smooth muscle cell function was assessed by eliciting a dose response curve to noradrenaline. Endothelial cell function was assessed by measuring the degree of endothelial-dependent relaxation of sub-maximally contracted vein samples. Iopamidol and iloprost did not have any deleterious effect on endothelial or smooth muscle cell function. Papaverine did not affect endothelial-dependent relaxation but did produce a significant decrease in smooth muscle contraction. The use of these intraoperative agents during femorodistal bypass does not appear to cause functional injury to the endothelial or smooth muscle cells.

Aged↗
PubMed1992

Contraction and relaxation of human internal mammary artery after intraluminal administration of papaverine.

The internal mammary artery has become the conduit of choice for coronary artery bypass grafting. Intraluminal papaverine treatment during operation reduces vasospasm and facilitates anastomosis. However, it has been suggested that papaverine may cause intimal damage, and accordingly we have investigated endothelial damage by comparing the responsiveness of internal mammary arteries before and after intraluminal exposure to papaverine (15 mg/mL). Control and papaverine-treated segments of internal mammary artery were obtained from 13 patients undergoing coronary artery bypass grafting and mounted as ring preparations in an organ bath. Cumulative dose contractions to noradrenaline were performed, and the dose producing a half maximal response was determined. Relaxation studies of submaximally contracted arteries were performed using the endothelium-dependent vasodilators acetylcholine and bradykinin and the endothelium-independent vasodilator sodium nitroprusside. In the human internal mammary artery the use of intraluminal papaverine increased the lumen size by 20% (p less than 0.05), and the contractions elicited by noradrenaline were significantly less in the papaverine group than in the control group (p less than 0.05). Endothelium-dependent relaxation to acetylcholine or bradykinin was not affected by papaverine treatment. Endothelium-independent relaxation was the same in both groups, with almost 100% relaxation achieved by sodium nitroprusside. These results indicate that intraluminal papaverine treatment during coronary artery bypass grafting causes a reduction of smooth muscle contraction and does not impair endothelium-dependent relaxation.

Acetylcholine↗
PubMed1992

Endothelial cell injury secondary to surgical preparation of reversed and in situ saphenous vein bypass grafts.

Failure of infra-inguinal vein grafts appears to be due to the development of intrinsic lesions (intimal hyperplasia, fibrous stenoses) within the graft which lead to narrowing of the lumen, poor blood flow and thrombosis. The cause of these lesions remains unknown but recently it has been suggested that endothelial injury might be an aetiological factor. The damage that can occur after preparation of reversed vein grafts includes loss of endothelial cells and functional impairment of those cells that remain, in that the ability to produce prostacyclin and endothelium-derived relaxing factor (EDRF) is reduced. The preparation of in situ grafts is different to that for reversed grafts in that a valvulotome is passed along the lumen of the vein to destroy the valves. However, little is known about the degree of endothelial injury that this technique causes. Vein samples were obtained from patients undergoing infra-inguinal and coronary artery bypass grafting. The veins were mounted in an organ bath system to measure isometric tension and exposed to the endothelium-dependent agents acetylcholine, bradykinin, adenosine, histamine and the endothelium-independent agent sodium nitroprusside. The results indicate that preparation of reversed vein grafts leads to some loss of endothelial cells with functional impairment of the cells that remain. However, preparation of in situ grafts leads to severe or total loss of endothelial cells which resulted in an absence of detectable EDRF release. These findings were confirmed by histological examination of the vein samples.

Aged↗
PubMed1992

Angiotensin-converting enzyme inhibition as first-line treatment for hypertension.

1. Perindopril (4 mg) was compared with atenolol (50 mg), captopril (25 mg b.d.) or a diuretic (hydrochlorothiazide 50 mg and amiloride 5 mg) in three studies involving a total of 503 hypertensive patients with a diastolic blood pressure (DBP) of 95-125 mmHg. 2. A 4 week single-blind placebo period preceded 12 weeks of active treatment. Dose titration was at weeks 4 and 8 if supine DBP greater than 90 mmHg. The dose was doubled and if necessary a diuretic was added in the atenolol or captopril comparisons, and atenolol was added in the diuretic study. 3. The fall in supine blood pressure (BP) was 27/17 mmHg with perindopril and 21/16 mmHg for atenolol. Monotherapy controlled 55% of patients on perindopril and 48% on atenolol, increasing to 78% and 58% with the addition of hydrochlorothiazide, respectively. Captopril caused a BP fall of 19/12 mmHg compared with 27/18 mmHg for perindopril, with 49% of both groups being controlled on monotherapy. 4. Diuretic addition produced a greater antihypertensive effect with perindopril (75%) compared with 57% for captopril in achieving control. Perindopril caused a comparable fall in supine BP to the diuretic combination 27/19 mmHg and 31/18 mmHg, but the fall in erect systolic BP was significantly greater for the diuretic. At 3 months, 85% of the diuretic group and 78% of the perindopril group achieved the target BP. 5. A multicentre trial of 856 patients treated with perindopril (690 patients treated for 1 year or more) has shown that BP control is maintained in the long term with a low incidence of side-effects (7.9%) causing withdrawal from treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗
PubMed1992

Experience with the Cardial inferior vena cava filter as prophylaxis against pulmonary embolism in pregnant women with extensive deep venous thrombosis.

OBJECTIVE: To report the use of the Cardial inferior vena caval filter as prophylaxis against pulmonary embolism in pregnant women with extensive iliofemoral thrombosis. SETTING: Leicester Royal Infirmary. SUBJECTS: Four pregnant women with extensive iliofemoral thrombosis, deemed to be at high risk of pulmonary embolism, managed over a period of one year. TECHNIQUE: In addition to standard full anticoagulation with heparin, the Cardial inferior vena cava filter was introduced percutaneously under local anaesthesia through the unaffected contralateral femoral vein and positioned in the inferior cava below the renal veins. RESULTS: The procedure was uncomplicated and did not compromise feto-maternal condition. There was no evidence of pulmonary embolism after filter insertion. CONCLUSION: The use of inferior vena cava filters should be considered as an adjunct to intravenous anticoagulation in pregnant women with extensive deep vein thrombosis of the lower limbs.

Adult↗
PubMed1992

Endothelium-dependent modulation of resistance vessel contraction: studies with NG-nitro-L-arginine methyl ester and NG-nitro-L-arginine.

1. The effect of NG-nitro-L-arginine methyl ester (L-NAME) and NG-nitro-L-arginine (L-NOARG) on noradrenaline (NA)-induced contractility and acetylcholine (ACh)-induced endothelium-dependent relaxation was studied in rat mesenteric resistance arteries. 2. Third order branches of mesenteric arteries were dissected and mounted on two forty micron wires in a Mulvany myograph. 3. Incubation with L-NAME and L-NOARG (10 microM) caused a time-dependent shift in the 50% response to NA (ED50) (0.01 microM-10 microM) but was not associated with an increase in the maximum contractile response. 4. L-NAME and L-NOARG (10 microM) caused a time-dependent inhibition of ACh (1 microM)-induced relaxation with a maximum effect after 120 min. 5. Following endothelium removal, incubation with either L-NAME or L-NOARG caused no significant shift in the ED50, although the residual relaxation response to ACh (1 microM) was further attenuated. 6. Incubation with the cyclo-oxygenase inhibitor, indomethacin, enhanced the relaxation to ACh and reduced the inhibitory effects of L-NAME and L-NOARG. 7. In conclusion, L-NAME and L-NOARG are potent inhibitors of acetylcholine-induced endothelium-dependent relaxation in mesenteric resistance arteries. The shift in ED50 associated with these inhibitors suggests a probable role for the endothelium in modulating the contractility of the resistance vasculature.

Acetylcholine↗