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B Jackson

Publications and source records attributed to B Jackson.

At least 127 records · Page 7Linked to original sources
PubMed1992

Mesenteric resistance and brain microvascular angiotensin-converting enzyme in the spontaneously hypertensive rat.

1. Angiotensin-converting enzyme (ACE) concentration was measured in mesenteric and brain microvessels from spontaneously hypertensive rats (SHR) and compared with normotensive controls using a specific radioligand binding assay. 2. Plasma angiotensin-converting enzyme activity was similar in SHR (n = 15) and normotensive controls (n = 21; 58 +/- 1 nmol HL/mL per min, vs 64 +/- 6 nmol HL/mL per min). 3. There was no significant difference between the mesenteric vascular angiotensin-converting enzyme radioligand binding site density (Bmax, fmol/mg protein) of SHR and normotensive controls (954 +/- 77 vs 890 +/- 56, P = 0.5, unpaired Student's t-test), despite significant differences in systolic blood pressure (220 +/- 8 mm Hg vs 120 +/- 6 mm Hg respectively, P less than 0.01) and increased mesenteric wet weight to bodyweight ratio in the hypertensive rats (0.28 +/- 0.02 mg/g, n = 5 vs 0.16 +/- 0.02 mg/g, n = 7, P less than 0.01). 4. Brain vascular angiotensin-converting enzyme radioligand binding site density (Bmax, fmol/mg protein) was also similar in SHR and normotensive controls (467 +/- 62, n = 5 vs 497 +/- 64, n = 5, P = 0.7, unpaired Student's t-test). 5. These results demonstrate that vascular angiotensin-converting enzyme concentration is not altered in the SHR and that vascular ACE is not increased in this form of vascular hypertrophy or regulated by the blood pressure level.

Animals↗
PubMed1992

Variation in angiotensin-converting enzyme (ACE) inhibitor affinity at two binding sites on rat pulmonary ACE: influence on bradykinin hydrolysis.

1. ACE from rat lung and testis was characterized by radioligand binding studies using [125I]-Ro 31-8472, the radioiodinated hydroxy derivative of the potent ACE inhibitor cilazaprilat. 2. Analysis of the displacement of [125I]-Ro 31-8472 from ACE by ACE inhibitors of different structure by the LIGAND program was best fitted by a two binding site model for lung ACE and a one binding site model for testis ACE. 3. There was marked variation in ACE inhibitor binding affinity at the two binding sites of lung ACE across the panel of ACE inhibitors studied (equilibrium dissociation constant; Kd; pmol/L) for site one vs site two: cilazaprilat 40 +/- 3 vs 430 +/- 92*; lisinopril 25 +/- 1 vs 848 +/- 107**; and quinaprilat 4 +/- 1 vs 1869 +/- 720; *P less than 0.05; **P less than 0.005, t-test, n = 3). Reduction in binding affinity at site two of lung ACE was related to an increase in ACE inhibitor side chain length or complexity of carboxyl terminal moiety. ACE inhibitor binding affinity at the testis ACE binding site resembled site one of lung ACE. 4. Inhibition of bradykinin hydrolysis by lung ACE in the presence of increasing concentrations of cilazaprilat or quinaprilat was similar (F = 0.64; P greater than 0.05), suggesting that bradykinin cleavage predominates at ACE active site one. 5. The differences in ACE inhibitor affinity at the two ACE active sites has implications in physiological substrate selectivity, and may influence the pharmacodynamic effects of different ACE inhibitors.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

The tissue renin-angiotensin system and its functional role.

1. The components of the renin-angiotensin system exist in many cardiovascular tissues (heart vessels, kidneys, adrenal glands). 2. Angiotensin-converting enzyme (ACE) is similar in somatic cells from all these sites. 3. ACE contains two catalytic sites that have different conformation requirements. This suggests that each site may have different substrates and that specific inhibitors could be developed for each site. 4. The cardiovascular functions of tissue ACE may include the regulation of regional blood flow, modulation of local sympathetic activity, stimulation of hyperplasia and hypertrophy and the mediation of inflammation.

Animals↗
PubMed1992

Acute and chronic effects of angiotensin-converting enzyme inhibitors on tissue angiotensin-converting enzyme.

1. The effects of angiotensin-converting enzyme (ACE) inhibitors on the tissue ACE were assessed by quantitative in vitro autoradiography after acute and chronic administrations of the drugs. 2. Following acute administration of lisinopril, perindopril or benazepril, ACE was markedly inhibited in the lung, kidney and blood vessels but not in the testis. In the brain, ACE was inhibited mainly in structures with a deficient blood brain barrier. 3. High doses of perindopril progressively inhibited ACE in other brain structures. Tissue ACE inhibition persisted after serum levels of the enzyme had returned to control levels. In the case of perindopril, the time course of tissue ACE inhibition correlated with the inhibition of the pressor responses to exogenous angiotensin I. 4. After chronic administration of lisinopril or perindopril for 14 days, a similar pattern of ACE inhibition was observed in the kidney, lung and blood vessels. In the lung, however, lisinopril was found to increase total ACE by 30%, while plasma ACE was increased two-threefold by both lisinopril and perindopril. Testicular ACE remained unaltered by chronic lisinopril treatment. 5. Overall, the changes in tissue ACE after the administration of inhibitors more closely parallel the drugs' biological effects than changes in plasma ACE or drug levels. ACE in the testis and brain is protected by permeability barriers that limit access of the drugs.

Administration, Oral↗
PubMed1992

Comparison of the pharmacokinetics and pharmacodynamics of perindopril, cilazapril and enalapril.

1. The pharmacokinetic and pharmacodynamic responses to enalapril, perindopril and cilazapril have been studied in essential hypertensives (2, 4 and 8 mg perindopril and 2.5 mg cilazapril, single dose and steady state) and normotensive volunteers (10 mg enalapril, single dose). 2. Plasma levels of the active diacid compounds reached similar peaks after single dose administration of the drugs. However, perindoprilat levels persisted for 5 days whereas cilazaprilat levels were not detectable beyond 12 h. 3. The higher levels of perindoprilat were associated with a greater inhibition of plasma angiotensin-converting enzyme (ACE) activity in both acute and steady state studies. 4. The potency of the active diacids in inhibiting plasma ACE activity was perindoprilat greater than cilazaprilat greater than enalaprilat. 5. There was a close relationship between plasma concentration, ACE inhibition and blood pressure decrease. Although both cilazapril and perindopril administration reduced blood pressure in hypertensive subjects, only perindopril exerted 24 h blood pressure control at the doses used.

Adult↗
PubMed1992

Reciprocal feedback regulation of kidney angiotensinogen and renin mRNA expressions by angiotensin II.

The present study asks whether angiotensin II (ANG II), a potent inhibitor of renal renin synthesis and release, regulates renal angiotensinogen synthesis. ANG II (or vehicle) was intravenously infused into male Sprague-Dawley rats for 3 days (vehicle or 100, 300, and 1,000 ng.kg-1 x min-1, n = 8/group), significantly increasing mean plasma ANG II concentrations and raising mean arterial blood pressure (MAP). ANG II dose dependently suppressed plasma renin concentration, kidney renin concentration, and renal renin mRNA levels. In contrast, ANG II infusion increased renal angiotensinogen mRNA levels stepwise to 122, 136 (P < 0.05), and 150% (P < 0.05) of control and also increased both liver mRNA levels (P < 0.05) and plasma angiotensinogen concentration (P < 0.05). Three days of angiotensin-converting enzyme inhibition (10 mg.kg-1 x day-1 quinapril in drinking water, n = 8) significantly decreased MAP (P < 0.05) and increased both mean plasma renin concentration (P < 0.05) and renal renin mRNA levels (P < 0.005). Plasma ANG II concentration tended to decrease (not significant), and neither renal nor hepatic angiotensinogen mRNA levels displayed significant difference. However, when data from ANG II-infused and quinapril-treated rats were analyzed together, correlation between plasma ANG II concentrations and renal angiotensinogen mRNA levels was highly significant (P < 0.005, r = 0.585). Thus plasma ANG II upregulates renal angiotensinogen gene expression and downregulates renal renin gene expression, a reciprocal feedback regulation that may have important physiological consequences.

Angiotensin II↗
PubMed1992

A case management system for infants with chronic illnesses and developmental disabilities.

Continuity of care has been identified as a priority goal for infants with developmental disabilities or chronic illnesses who are faced with long-term or frequent hospitalizations. This goal was accomplished by Project Continuity, a family-centered intervention and care coordination system in which the family plays an integral role in the planning and implementation of the care plan. Procedures borrowed from diverse traditions including job analysis from industrial psychology and quality assurance from health care were used to describe, monitor, and assess the complex professional behaviors and outcomes of care coordination.

Child Health Services↗
PubMed1992

Systemic and renovascular hypertension.

To ascertain the contribution of systemic hypertension in the progression of renal failure, we have studied the effects of pharmacological treatment of hypertension in rats with the remnant kidney model of renal insufficiency, streptozotocin diabetes, or nephrotoxic serum nephritis. Treatment with the angiotensin converting enzyme (ACE) inhibitor enalapril lowered systemic blood pressure in the remnant kidney and diabetic animals, but did not lower blood pressure in rats with nephrotoxic serum nephritis. Proteinuria was reduced in all three models, and creatinine clearance improved in the remnant kidney and diabetic animals, when compared with untreated controls. In the remnant kidney and diabetic models systemic blood pressure was lowered to a similar degree by treatments with a calcium blocker, with no improvement in either proteinuria, or glomerular filtration rate. Further studies of the long-term effects of enalapril have been undertaken in rats with the two kidney one clip model of hypertension. Rats treated with enalapril had a lower blood pressure and improved survival over one year of treatment, compared with untreated rats. After 1 year of treatment however the clipped kidney was small and fibrotic, and non functional. Following withdrawal of enalapril therapy there was no functional improvement of the clipped kidney. The possibility that ACE inhibitors have a specific intra-renal effect reducing the rate of progression of renal disease now needs confirmation in human studies. In renovascular hypertension however, intra-renal changes induced by ACE inhibitors may cause irreversible renal damage.

Animals↗
PubMed1992

Money matters.

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Accounts Payable and Receivable↗
PubMed1992

Two binding sites on angiotensin-converting enzyme: evidence from radioligand binding studies.

Purified angiotensin-converting enzyme (ACE) from rat lung and testis, membrane preparations of ACE from lung, kidney, and testis, and ACE from plasma were used in radioligand binding studies, to seek evidence for two binding sites in ACE of somatic origin, as predicted by molecular biology studies. 125I-Ro 31-8472, a radioiodinated hydroxy derivative of cilazaprilat, and 125I-351A, a radioiodinated p-hydroxybenzamidine analogue of lisinopril, were used as radioligands. Autoradiographic study of renal ACE using 125I-Ro 31-8472 or 125I-351A showed the same distribution of radioligand binding across kidney sections and identical radioligand binding for purified lung and testis ACE by Western blot, confirming that the same protein bound both radioligands. Analysis of displacement of 125I-Ro 31-8472 binding from ACE by ACE inhibitors 351A and lisinopril yielded biphasic curves for pulmonary, renal, and plasma ACE and a monophasic curve for ACE from the testis. Analysis by LIGAND suggested two binding sites in ACE from plasma or somatic sources and one binding site in ACE of testicular origin, as predicted by molecular biology studies. Displacement of 125I-351A binding from lung and testis ACE by Ro 31-8472 and 351A was monophasic. LIGAND analysis revealed interaction with a single class of binding sites on lung and testis ACE, in agreement with previous studies using 125I-351A. Equilibrium dissociation constants (Kd) for the carboxyl-terminal (KdI) and amino-terminal (KdII) binding sites of purified ACE, using 125I-Ro 31-8472, were similar for Ro 31-8472 (lung kdI, 65 +/- 7 pM; KdII, 175 +/- 38 pM) but were clearly different for 351A (lung KdI, 19 +/- 2 pM; KdII, 2771 +/- 489 pM; p less than 0.01). Cell membrane-associated somatic ACE and plasma ACE, which is devoid of a carboxyl-terminal hydrophobic anchor region, had similar absolute values and differences in 351A binding affinities at the two ACE binding sites. Kd in testis was 46 +/- 6 pM for Ro 31-8472 and 16 +/- 3 pM for 351A, corresponding to estimates at the carboxyl-terminal binding site of somatic ACE. The 65-200-fold reduction in 351A binding affinity at the amino binding site may limit the detection of two binding sites on somatic ACE by 125I-351A radioligand binding analysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Cardiac risk factor management. Experience of an outpatient hypertension clinic.

OBJECTIVE: To describe the outcome of the management of cardiovascular risk factors in the hypertension clinic of a teaching hospital over a five-year period. DESIGN: Retrospective analysis of risk factor data (blood pressure, plasma cholesterol level, body weight, smoking and drinking habits) obtained from computerised hypertension clinic progress report forms. SETTING: Public teaching hospital. PATIENTS: One hundred and thirty-one patients referred to the clinic from both general practice and from within the hospital who attended the clinic regularly during the five-year study period. INTERVENTION: Long term management of hypertension and coexisting coronary risk factors by dietary, medical and lifestyle intervention. RESULTS: There was a significant improvement in diastolic blood pressure control in 1990 versus 1986 in both men and women, while systolic blood pressure improved in women only. The number of patients controlled with monotherapy increased from 38% in 1986 to 45% in 1990. Eighty-nine per cent of the men and 85% of women remained above their maximum desirable weight. Reported levels of alcohol consumption were low and the proportion of smokers was below that of the general population. A significant decline in plasma total cholesterol levels was observed in the women. Despite dietary advice and a limited use of lipid lowering drugs, 53.2% of the men and 66.1% of the women continued to have total plasma cholesterol levels above 5.5 mmol/L in 1990. High density lipoprotein levels increased significantly in the women only. CONCLUSION: A high proportion of our clinic patients have well controlled hypertension, but the clinic program produced little evidence of improvement in risk factors in men stabilised by long term therapy. More intensive methods of achieving lifestyle modification and a wider use of lipid lowering drugs may be needed if we are to achieve satisfactory body weights and lipid profiles in hypertensive patients.

Ambulatory Care Facilities↗
PubMed1991

Felodipine in combination with a beta-adrenoceptor blocker as an effective substitute for triple therapy in severe hypertension. The Australian Felodipine Multicentre Study Group.

We have studied the efficacy and tolerability of felodipine plus a beta-adrenoceptor blocker in 79 patients with essential hypertension previously treated with a combination of three or more anti-hypertensive agents, one of which was a beta-adrenoceptor blocker. After a 4-week run-in period on the same beta-blocker plus placebo (as a substitute for the other agents in the regimen), felodipine was added and its dose titrated to achieve a supine diastolic blood pressure or less than 90 mm Hg. This was followed by a 12-week maintenance phase in all patients, and 47 patients entered an optional long-term follow-up for an additional 9 months. The mean supine blood pressure was 149/88 mm Hg at entry and 174/108 mm Hg after the run-in phase. Felodipine significantly reduced the blood pressure to 142/85 mm Hg after dose titration and to 141/84 mm Hg after 12 weeks, 94% of patients achieving a supine diastolic blood pressure of 90 mm Hg or below. This reduction was maintained in the patients who were followed for 12 months. The adverse events recorded were usually mild, transient, and typical for an effective precapillary vasodilator. Nine of 74 patients (11%) were withdrawn in the first phase of the study because of adverse events and 5 of 47 patients were withdrawn during the long-term follow-up. These results show that the efficacy and tolerability of a combination of felodipine with a beta-blocker allow a simplified regimen for hypertensive patients who were previously taking three or more drugs for satisfactory blood pressure control.

Adolescent↗
PubMed1991

Cholesterol lowering and bile acid excretion in the hamster with cholestyramine treatment.

Cholestyramine was administered to hamsters at 6 doses in the diet for 1 week. Plasma cholesterol, LDL + VLDL cholesterol and HDL cholesterol were measured after this period. Bile acid excretion was measured in faeces collected over the final 24 h of the experiment. A dose-response curve for each parameter measured was constructed using data from individual hamsters. For the bile acid and the cholesterol measurements a maximum response was observed at the highest doses. A correlation between the bile acids excreted over 24 h and the LDL + VLDL cholesterol showed that the maximum effect of cholestyramine on lowering plasma and lipoprotein cholesterol occurred at a submaximal excretion level of bile acids. Comparison of the efficiency of cholestyramine in reducing plasma cholesterol in the hamster with limited data in the dog and in man suggest that a greater lowering of plasma cholesterol is achieved in the dog and in man for an equivalent increase in bile acid excretion caused by the sequestrant. As is already known, cholestyramine treatment caused an increase in hepatic cholesterol 7 alpha-hydroxylase and HMG-CoA reductase activity. Interestingly in this study the novel observation was made that the bile acid sequestrant reduced the activity of hepatic acyl-CoA: cholesterol acyltransferase.

Animals↗
PubMed1991

Acute and chronic effects of perindopril on tissue angiotensin converting enzyme activity.

The pattern of inhibition of tissue angiotensin converting enzyme (ACE) was studied in rats after acute and chronic (14 days) oral administration of perindopril. Free and total tissue ACE were measured by quantitative in vitro autoradiography using [125I]-351A as a radioligand and compared with plasma ACE and pressor responses to angiotensin I. Following oral perindopril, plasma perindoprilic acid and the pattern of inhibition of plasma ACE activity were maximal at 1 to 2 h, but recovered over 24 h. However, inhibition of the pressor response to angiotensin I was more prolonged, being 95% at 4 h, but had not fully recovered by 24 h. Acutely, ACE was markedly inhibited in renal proximal tubules, lung parenchyma, and aortic wall. At 24 h, ACE in these tissues had only partially recovered. Angiotensin converting enzyme in vascular endothelium of other organs showed a similar pattern of inhibition. In contrast, ACE in testicular seminiferous tubules was unaffected by perindopril. After chronic (14 days) administration of perindopril, total plasma ACE increased 3-fold, of which 49% was occupied by the inhibitor. Total tissue ACE in kidney and aorta did not change, and the pattern of inhibition observed acutely was maintained during chronic treatment. These results demonstrate a prolonged effect of ACE inhibitors on tissue ACE that may better explain the time course of these drugs than the changes in plasma ACE or plasma levels of the drugs.

Angiotensin I↗
PubMed1991

Measurement of angiotensin converting enzyme induction and inhibition using quantitative in vitro autoradiography: tissue selective induction after chronic lisinopril treatment.

Angiotensin converting enzyme (ACE) inhibitors lead to induction of ACE in animals and humans. This complicates the use of ACE enzymatic activity as an index of inhibition in plasma or tissues after chronic administration of ACE inhibitors. We have, therefore, developed a method for ACE measurement by in vitro autoradiography using an 125I-labelled inhibitor to quantitate total ACE and the concentration of free (not inhibited) ACE in tissues after prolonged administration of ACE inhibitors to rats. Measurements made on unprocessed tissue sections reflect residual free ACE activity in the presence of the unlabelled inhibitor. In a parallel series of adjacent sections, the ACE inhibitor is dissociated from the enzyme by reversibly denaturing the enzyme by zinc chelation. This is followed by reconstitution of the active enzyme by zinc ion replacement and measuring total enzyme concentration. This technique permits measurement of the extent of ACE inhibition and induction. This method was evaluated in tissues of rats following chronic oral administration of lisinopril (10 mg/kg per day) for 2 weeks. The pattern of ACE inhibition was similar to that seen in our previous acute studies. However, induction of ACE was found to be organ specific; plasma total ACE increased 1.75-fold and total ACE in the lung increased by 30% compared with untreated animals, but there was no demonstrable change in total ACE concentration in the kidney, adrenal or aorta. Despite this, during chronic treatment with lisinopril, ACE activity in all of these organs was inhibited with low levels of free ACE.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗