Search PubMed⌕ Search

Biomedical subjects

J L Reid

Publications and source records attributed to J L Reid.

At least 91 records · Page 5Linked to original sources
PubMed1994

Responses to low dose intravenous perindoprilat infusion in salt deplete/salt replete normotensive volunteers.

1. Intravenous ACE inhibitor therapy appears to have a role in the treatment of acute heart failure and early after myocardial infarction. Practical experience with intravenous administration with activation of renin is limited. We report responses to perindoprilat (Pt, 0.67 mg) or placebo (P) infused over 4 h in normotensive male volunteers (n = 12, 19-28 years, 53-77 kg) with double-blind, placebo controlled salt depletion (SD) or salt repletion (SR) as a model of the activated renin system. 2. Salt depletion caused no significant fall in serum sodium (P, 139.4 +/- 2.4; Pt, 138.3 +/- 1.9) compared with salt replete preparation (P, 139.9 +/- 1.2; Pt, 139.7 +/- 0.9) but elevation of plasma renin activity 2-3-fold. Pretreatment baseline systolic blood pressure following salt depletion (P, 121 +/- 9.3/71 +/- 7.9; Pt, 121.5 +/- 9.6/69 +/- 8.1) was higher than following salt replete preparation (P, 114 +/- 9.5/61 +/- 7.2; Pt, 116.9 +/- 6.9/67 +/- 7.2). 3. Baseline corrected supine SBP fell significantly and to a similar extent following active treatment regardless of activation of the renin system (SD, -14.6 +/- 9.5/-9.4 +/- 6.4; SR, -12 +/- 14/-10.1 +/- 6.6) compared with placebo (SD, -6.1 +/- 6/-3.7 +/- 5.6; SR, -4.7 +/- 10/-1.3 +/- 6.5). Heart rate was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Chronic exposure of cultured bovine endothelial cells to oxidized LDL abolishes prostacyclin release.

We investigated the effect of chronic exposure (3 days) with low-density lipoprotein (LDL) and oxidized (Ox)-LDL on the unstimulated and stimulated formation of prostacyclin (6-keto-prostaglandin [PG]F1 alpha) and total inositol phosphates (IPs) by cultured bovine aortic endothelial cells. Neither basal nor bradykinin-stimulated (1 to 10 nmol/L) formation of 6-keto-PGF1 alpha was affected by LDL, except at the highest concentration of bradykinin tested (100 nmol/L). In the presence of the antioxidants N-acetyl-L-cysteine (NAC, 10 mumol/L) or vitamin E (100 mumol/L), basal and bradykinin-stimulated formation of 6-keto-PGF1 alpha was potentiated by 20 micrograms protein/mL of LDL. Ox-LDL decreased unstimulated formation of the eicosanoid from 3.1 +/- 0.2 pg/micrograms protein in control cells to 1.6 +/- 0.1 and 0.5 +/- 0.1 pg/microgram protein after 3-day incubation with 5 and 20 micrograms protein/mL of Ox-LDL, respectively (P < .05). As in the basal state, Ox-LDL decreased bradykinin-induced 6-keto-PGF1 alpha formation. NAC or vitamin E did not influence Ox-LDL-induced endothelial cell changes in eicosanoid production. IPs formation by endothelial cells increased to a similar extent in the presence of 20 micrograms protein/mL of either LDL or Ox-LDL. However, no change was apparent in the bradykinin (10 mumol/L)-induced increase in total IPs formation after incubation with the lipoproteins. The data indicate that chronic exposure to Ox-LDL abolishes the production of prostacyclin by cultured endothelial cells. The oxidatively modified lipoprotein seems to more specifically affect the prostacyclin pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Phosphoinositide metabolism and aging in aorta from SHR and WKY rats: effects of endothelin-1 and noradrenaline.

Inositol phosphate formation in aortic rings from SHR and WKY rats of different ages (6, 14, and 40 weeks) was examined. Both basal and agonist (noradrenaline and endothelin-1) stimulated levels of inositol phosphates were studied. No differences in basal levels of inositol phosphate formation were observed between SHR and WKY nor were differences in agonist stimulated levels found in 6 week old animals. However, at 14 and 40 weeks both noradrenaline and endothelin-1 stimulated levels were reduced in SHR compared to WKY. Both endothelin and noradrenaline stimulated inositol phosphate formation decreased with age in SHR. In WKY there was a decrease in endothelin but not noradrenaline stimulated levels with age. Age related decreases were consistently greater in SHR than WKY. Thus, both age and rat strain modulated agonist stimulated inositol phosphate formation.

Aging↗
PubMed1994

Coordinating and standardizing long-term care: evaluation of the west of Scotland shared-care scheme for hypertension.

BACKGROUND: The long-term management of patients with chronic conditions such as hypertension presents problems for the health services. Shared care addresses these by coordinating care and defining responsibilities. AIM: This study set out to investigate the feasibility, acceptability and cost effectiveness of shared general practitioner-hospital care for well-controlled hypertensive patients in an urban area by comparing three matched groups of patients. METHOD: A total of 554 outpatient clinic attenders, considered suitable for shared care by their consultant, were randomly allocated to shared care or follow up in the outpatient clinic; a third group of 277 patients was selected from a nurse practitioner clinic. Main outcome measures were the proportion of patients in the second year of follow up who had undergone a complete review (blood pressure measurement, serum creatinine level result and electrocardiograph report), acceptability to patients and general practitioners as assessed by questionnaire, and cost per complete review in year two (National Health Service and patient costs). RESULTS: After two years 220 (82%) shared care patients had had a complete review compared with 146 (54%) outpatient clinic attenders and 202 (75%) nurse practitioner clinic attenders. Blood pressure control was similar in each group. Of 297 general practitioners invited, 85% wished to participate in the study; 61% of questionnaire respondents subsequently wanted shared care to continue while 25% were unsure. Half of the patients receiving shared care preferred this method of follow up. The rank order of cost-effectiveness ratios was shared care, nurse practitioner care and conventional outpatient care, relative differences being most marked when only patient costs were considered. CONCLUSION: Shared care for hypertension is feasible in an urban setting, acceptable to the majority of participants and is a cost-effective method of long-term follow up.

Chronic Disease↗
PubMed1993

Down-regulation of imidazoline sites in rabbit kidney.

The effects of 6 days treatment with guanabenz, clonidine, rilmenidine and idazoxan on [3H]idazoxan and [3H]clonidine binding to imidazoline sites on rabbit kidney membranes were compared. Guanabenz and rilmenidine treatment resulted in a decrease in Bmax for [3H]clonidine binding and guanabenz treatment for [3H]idazoxan binding consistent with the compounds in vitro affinities for the imidazoline binding sites. [3H]Idazoxan binding was also decreased by idazoxan treatment suggesting that idazoxan may act as an agonist at this site. These results show that imidazoline sites in kidney may be modified during chronic drug treatment and provide further evidence for differences between the sites labelled by the two ligands.

Adrenergic alpha-Agonists↗
PubMed1993

Blood pressure response to the first dose of angiotensin-converting enzyme inhibitors in congestive heart failure.

Angiotensin-converting enzyme (ACE) inhibitors improve survival in heart failure and delay progression to clinical heart failure in patients with left ventricular dysfunction after myocardial infarction. Increasing numbers of older patients are being considered for such treatment. However, there are reports of excessive and prolonged decreases in blood pressure (BP) after the first dose of some ACE inhibitors. We have studied the hemodynamics, pharmacokinetics, and neurohumoral responses to the first dose of oral captopril 6.25 mg, enalapril 2.5 mg, perindopril 2.0 mg, intravenous enalaprilat 1.5 mg, and perindoprilat 1.0 mg, compared with oral or intravenous placebo in 6 parallel groups of 12 elderly patients each with moderate-to-severe (New York Heart Association classes II-IV) heart failure. Oral dosing with active drugs led to different temporal responses. After captopril, there was an early short-lived decrease in BP. Enalapril led to a later long-lasting decrease, but perindopril was not different from placebo. Intravenous enalaprilat and intravenous perindoprilat each lowered BP to a similar extent. The doses of drugs used appeared to be comparable because plasma ACE inhibition was similar following perindopril or enalapril and also comparing perindoprilat and enalaprilat. These studies indicate that oral ACE inhibitors have different profiles of acute BP changes after the first dose. The explanation is not clear, but could include physicochemical differences in the interaction between prodrug ester and diacid metabolites leading to differences in tissue distribution and local enzyme inhibition.

Aged↗
PubMed1993

The pharmacodynamics and pharmacokinetics of the combination of nifedipine and doxazosin.

In a single-blind study 12 normotensive men took nifedipine 20 mg (Group 1, n = 6) or doxazosin 2 mg (Group 2, n = 6), followed by the combination. Each subject attended on four 9-h study days for evaluation of the effects of single and multiple doses of the monotherapy and the effects of adding single and multiple doses of the second drug. Measurements of BP, HR, plasma drug concentrations, and apparent liver blood flow were recorded. The combination was generally well tolerated. BP was consistently lower with the combination than with either monotherapy: for example, average erect BP was 108/61 (Group 1) and 112/62 mmHg (Group 2) compared with 122/66 and 116/68 during steady-state monotherapy. The introduction of nifedipine in Group 2 was associated with a significant increase in liver blood flow at 1.5 h: 1560 vs 1050 ml.min-1 during monotherapy with doxazosin. There was no significant kinetic interaction. In particular, the steady-state AUC of doxazosin was unaffected by the addition of nifedipine: 257, 307, 301, and 256 ng.ml-1.h for the 4 study days (Group 2).

Adult↗
PubMed1993

Analysis of biogenic amines in plasma of hypertensive patients and a control group.

Procedures were developed for the determination of 17 circulating amines using gas chromatography-negative ion chemical ionisation mass spectrometry. The amines were quantified against their appropriate deuterated isotopomers. The mean concentrations and ranges of catecholamines and trace amines were high compared with previous studies. In comparison with nonhypertensives, plasma from hypertensives had higher concentrations of the following amines: noradrenaline (t = 4.0%); normetanephrine (t = 6.1%) and metanephrine (t = 1.9%). There were no significant differences between 5HT levels in plasma from hypertensives and controls. The following trace amines could be detected in variable amounts in plasma: p-tyramine, m-tyramine, p-octopamine, m-octopamine, p-synephrine, m-synephrine, and salsolinol. The trace amines melatonin, N-acetyl 5HT, tryptamine, 6-hydroxymelatonin and 5-methoxytryptamine could not be detected in plasma with limits of detection lying in the range 20-100 pg ml-1.

Biogenic Amines↗
PubMed1993

Angiotensin-converting enzyme inhibitors in heart failure: blood pressure changes after the first dose.

Angiotensin-converting enzyme (ACE) inhibitors prevent the formation of angiotensin II in the circulation and a range of tissues. ACE inhibitors not only are effective, well-tolerated antihypertensive drugs but also improve symptoms and signs in patients with congestive cardiac failure. In addition, they improve long-term survival in these latter patients. Although ACE inhibitors are relatively free of side effects in patients with heart failure, hypotension after the first dose has been reported that may lead to symptomatic renal, cardiac, or cerebral hypoperfusion. Most reports have been uncontrolled and anecdotal. We report a double-blind placebo-controlled study in a parallel group of patients with cardiac failure (New York Heart Association classes II through IV). In total, 72 patients (6 groups of 12) were studied after either placebo, captopril, 6.25 mg, enalapril, 2.5, or perindopril, 2 mg orally, enalaprilat 1.5 mg, or perindoprilat, 1.0 mg intravenously. The blood pressure responses differed between the groups, with a short-lived early fall after captopril and a long-lasting fall after enalapril, whereas perindopril was no different from placebo. There was no significant difference between the two active intravenous regimens. Plasma ACE measurements suggested that the relative doses used were at least comparable. Further studies are in progress to investigate the mechanisms underlying the differential hemodynamic responses and also to explore the clinical relevance to safety and efficacy in the management of heart failure.

Acetylcholinesterase↗
PubMed1993

Neuropeptide Y-induced inositol phospholipid hydrolysis in blood vessels from normotensive and spontaneously hypertensive rats.

1. Neuropeptide Y (NPY) increased inositol phosphate (IP) formation in the femoral artery and vein of adult Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. 2. Noradrenaline (NA, 10(-6) M) induced IP accumulation in both strains of rats. 3. Subthreshold concentrations of NPY (3 x 10(-9) M for femoral vein and 10(-8) M for femoral artery) failed to modify NA (10(-6) M)-induced IP formation in both vessels. 4. These results suggest that the direct contractile effects but not the potentiation of NA-induced contractions may be directly linked to phosphatidylinositol turnover in adult SHR and WKY rats.

Animals↗
PubMed1993

Endothelin-1-induced reductions in cerebral blood flow: dose dependency, time course, and neuropathological consequences.

The capacity of endothelin-1 to induce severe reductions in cerebral blood flow and ischaemic neuronal damage was assessed in anaesthetised rats. Endothelin-1 (25 microliters of 10(-7)-10(-4) M) was applied to the adventitial surface of an exposed middle cerebral artery and striatal blood flow assessed by the hydrogen clearance technique. Endothelin-1 induced severe dose-dependent reductions in cerebral blood flow (e.g., minimum CBF at 10(-5) M of 9 +/- 11 ml 100 g-1 min-1 compared to 104 +/- 22 ml 100 g-1 min-1 with vehicle, p < 0.05), which persisted for at least 60 min at each concentration of endothelin-1. Application of endothelin-1 to the middle cerebral artery produced dose-dependent ischaemic brain damage (e.g., volume of damage of 65 +/- 34 mm3 at 10(-5) M compared to 0.22 +/- 0.57 mm3 for vehicle, p < 0.01). These data demonstrate that endothelin-1 is capable of reducing blood flow to pathologically low levels and provide a new model of controlled focal ischaemia followed by reperfusion.

Animals↗
PubMed1993

Haemodynamic and hormonal responses to losartan (DuP753/MK954) infusion during cardiac catheterization in conscious salt-deplete dogs.

1. Haemodynamic and hormonal responses to infused angiotensin II were studied in conscious salt-deplete dogs during infusion of D-glucose or losartan (DuP753/MK954). 2. Mean arterial pressure (118 +/- 13 mmHg) fell rapidly after losartan (60 min 106 +/- 18 mmHg) with a rise in heart rate (107 +/- 16 beats/min) from baseline (98 +/- 17 beats/min). Pressor responses to angiotensin II during D-glucose infusion (6 ng min-1 kg-1, 99 +/- 10 mmHg; 18 ng min-1 kg-1, 140 +/- 15 mmHg; 54 ng min-1 kg-1, 157 +/- 12 mmHg; 162 ng min-1 kg-1, 178 +/- 14 mmHg) showed a parallel shift during losartan infusion with very similar pressures in response to higher rates of angiotensin II infusion (54 ng min-1 kg-1, 108 +/- 17 mmHg; 162 ng min-1 kg-1, 138 +/- 14 mmHg; 486 ng min-1 kg-1, 155 +/- 14 mmHg; 1458 ng min-1 kg-1, 177 +/- 12 mmHg). Losartan caused a fall in baseline systemic vascular resistance. Despite the similar mean arterial pressure, the rise in systemic vascular resistance after angiotensin II during D-glucose infusion (162 ng min-1 kg-1, 8065 +/- 1967 dyn s cm-5) was reduced during losartan infusion (1458 ng min-1 kg-1, 6645 +/- 1720 dyn s cm-5. Losartan caused a small rise in cardiac output related to a rise in heart rate and increased stroke volume. Pressure infusions of angiotensin II caused a fall in cardiac output during D-glucose infusion, which was blocked during losartan infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗
PubMed1993

Lateral diffusion and fatty acid composition in vascular smooth muscle membrane from stroke-prone spontaneously hypertensive rats.

We measured membrane fluidity and fatty acid composition in cultured vascular smooth muscle cells from stroke-prone spontaneously hypertensive and Wistar-Kyoto normotensive rats. Membrane fluidity was measured as a lateral diffusion of 5 N (octadecanoyl) aminofluorescein using fluorescence microscopy and fluorescence recovery after photobleaching. Fatty acid composition of membrane fractions was measured using high performance liquid chromatography. Lateral diffusion was significantly lower (the membrane had lower fluidity) in vascular smooth muscle cells from stroke-prone spontaneously hypertensive rats as compared to those cells isolated from Wistar-Kyoto reference strain. The ratio of arachidonic acid to total fatty acids was 0.058 +/- 0.007 in the plasma membrane from stroke-prone spontaneously hypertensive rats and 0.036 +/- 0.005 in that from Wistar-Kyoto rats, P = .005. Similarly, the ratios of arachidonic to oleic acid and arachidonic to palmitic acid were significantly greater in cells from stroke-prone spontaneously hypertensive rats (P = .002 for difference in each ratio). These results show decreased lateral diffusion (decreased membrane fluidity) in vascular smooth muscle cells from stroke-prone spontaneously hypertensive rats. This is associated with increased content of arachidonic acid, the major precursor of prostaglandins and other eicosanoids. We postulate that local changes in the unsaturated fatty acid composition related to arachidonic acid storage and release contribute to reduced membrane fluidity in stroke-prone spontaneously hypertensive rats.

Animals↗
PubMed1993

Membrane microviscosity does not correlate with blood pressure: a cosegregation study.

OBJECTIVE: To determine whether elevated microviscosity is associated with elevated arterial pressure in segregating (F2) hybrids produced by crossing stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats. METHODS: SHRSP and WKY rats were obtained from the colony at the University of Heidelberg. F2 progeny were obtained by brother-sister mating of the F1 progeny of the cross between SHRSP and WKY rats. Membrane microviscosity (the inverse of fluidity) was measured as a fluorescence anisotropy of trimethylammonium diphenylhexatriene incubated with the erythrocyte membranes. The measurements were made using a luminescence spectrometer with computer-controlled excitation and emission polarizers. RESULTS: Membrane microviscosity was significantly greater (fluidity was lower) in erythrocyte membranes obtained from SHRSP than in those obtained from WKY rats. In the F2 cohort there were no significant correlations between membrane microviscosity and systolic blood pressure, diastolic blood pressure, salt-loaded systolic blood pressure or salt-loaded diastolic blood pressure. A similar lack of relationship between these parameters was shown in a subgroup analysis, in which males or females with a male WKY rat progenitor and males or females with a male SHRSP progenitor were analysed separately. CONCLUSIONS: Erythrocyte membrane microviscosity is elevated in SHRSP compared with WKY rats. In segregating F2 hybrid rats the membrane microviscosity trait does not correlate with blood pressure. These results eliminate the microviscosity trait as being directly related to the cause of genetic differences in blood pressure between WKY rats and SHRSP.

Animals↗
PubMed1993

Differences between calcium antagonists: duration of action and trough to peak ratio.

UNLABELLED: Comparison of first- and second-generation calcium antagonists: Despite their diversity of structure, the first-generation calcium antagonists nifedipine, verapamil and diltiazem all have a short elimination half-life and a relatively short duration of action. In contrast, there appears to be wide diversity in these properties among the newer calcium antagonists, which are mostly dihydropyridines. The longer half-life and physicochemical properties of some of the newer agents allow full 24-h blood pressure control. Duration of action of lacidipine: Taken only once a day, lacidipine has proved as potent an antihypertensive agent as slow-release nifedipine administered twice a day. Lacidipine produces a satisfactory fall in blood pressure not only during waking hours but also during sleep at night, as shown by 24-h ambulatory monitoring. Moreover, this blood pressure fall is obtained without any reflex tachycardia or associated side effects. Compared with patients treated with placebo, systolic and mean arterial blood pressure variability (standard deviation) is reduced by lacidipine treatment. CONCLUSIONS: Control of blood pressure using lacidipine once a day meets the criteria proposed by the United States Food and Drugs Administration for antihypertensive drug efficacy and duration of action.

Antihypertensive Agents↗