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Biomedical subjects

G W Boyd

Publications and source records attributed to G W Boyd.

At least 37 records · Page 2Linked to original sources

Structural change in the rat hindlimb during deoxycorticosterone acetate hypertension; its reversibility and prevention.

This study measured the time course of the development and reversal of structural change in resistance vessels during deoxycorticosterone acetate (DOCA) hypertension and after cessation of DOCA in Wistar rats by hindquarter perfusion. The relationship of structural change to blood pressure was further assessed by preventing hypertension during DOCA treatment with hydralazine. Blood pressure rose progressively during DOCA treatment reaching 198.6 +/- 2.0 (s.e.) mmHg at 10 weeks. Five weeks after the cessation of DOCA, when it had been given for 2 weeks, hypertension reversed completely but after 4, 8 and 10 weeks of treatment, post-DOCA reversal of hypertension was only partial. Hindquarter perfusion pressure at maximum vasodilatation and maximum vasoconstriction increased with increasing duration of DOCA treatment and reversed 5 weeks post-DOCA to a similar degree to the blood pressure with only partial reversal of both perfusion pressures and hypertension when DOCA had been given for 8 and 10 weeks. Hydralazine did not completely prevent heart hypertrophy in the DOCA rats and caused some cardiac hypertrophy in the control ('vehicle' only) rats, although it both prevented hypertension and evidence of vascular structural change in DOCA rats.

Animals↗

Histometric assessment of renal arterioles during DOCA and post-DOCA hypertension and hydralazine treatment in rats.

It is now well established that structural changes in resistance vessels contribute to the long-term maintenance of many forms of hypertension. This study measured the time course of structural change in smaller resistance vessels during the development of deoxycorticosterone acetates (DOCA) hypertension and after cessation of DOCA in Wistar rats by histometric assessment of cross-sections of renal arterioles. The relationship of structural change to blood pressure was assessed by preventing hypertension during DOCA treatment with hydralazine. Blood pressure rose progressively during DOCA treatment reaching 192 +/- 3 mmHg compared with 132 +/- 2 mmHg in controls after 10 weeks. Five and 10 weeks after cessation of DOCA, following 10 weeks of DOCA treatment, post-DOCA reversal of hypertension was only partial. Medial area to internal elastic lamina (IEL) radius ratio, wall to lumen ratio and intimal area to IEL radius ratio of renal arterioles increased progressively during 10 weeks of DOCA treatment with partial reversal of the increased medial area and wall to lumen ratio 5 weeks post-DOCA. Hydralazine completely prevented hypertension in DOCA rats and also largely prevented structural change.

Animals↗

Structural changes vary along individual arterioles in deoxycorticosterone acetate hypertensive rats.

The variability of structural changes along individual arterioles in deoxycorticosterone acetate (DOCA) hypertensive rats was measured by coefficients of variation of: (a) serial lumen diameters along microfil casts of individual mesenteric arterioles; and (b) wall and lumen indices in serial histological cross-sections along individual renal arterioles. The mean lumen diameter of third-order mesenteric arterioles decreased with increasing duration of hypertension. There was increased variability of lumen diameter along lengths of DOCA arterioles, the coefficient of variation at 10 weeks DOCA treatment being 20.2 +/- 0.6% compared to 9.2 +/- 0.2% in controls (P less than 0.001). Medial area to internal elastic lamina (IEL) radius ratio of renal arterioles was increased in DOCA rats compared with control rats (P less than 0.025) and its variability along individual arterioles expressed as the coefficient of variation was 31.70 +/- 3.87% in DOCA rats compared with 15.29 +/- 1.72% in controls (P less than 0.005). The observed increase in variability of lumen diameter and medial area along short lengths of individual arterioles in DOCA hypertensive rats indicates that hypertensive structural changes are probably not directly related to local blood pressure. We suggest that irregular functional vasoconstriction in hypertensive rats could account for this distribution of structural changes.

Animals↗

Effect of sire and sexual experience on serving capacity of yearling beef bulls.

Two experiments were conducted in successive years on a Kansas ranch to determine 1) if serving capacity could be evaluated in virgin yearling beef bulls under field conditions, 2) the influence of sire on serving capacity, and 3) the effect of sexual experience on subsequent serving capacity for low serving capacity bulls. In Experiments 1 and 2, 70 and 78 Angus bulls 13 to 15 mo old representing four and six different sires, respectively, were used. In both experiments, a pretest session that measured reaction time to service preceded two successive serving capacity tests. Following the first serving capacity test, in Experiment 2, all low serving capacity bulls (n = 23) underwent sexual experience school, which consisted of exposure to nonrestrained estrus-induced females over a 4-d period. Five days after sexual experience school (9 d after the first serving capacity test), all Experiment 2 bulls were retested. In both experiments, sire influenced mean serving capacity scores of sons (P < 0.01, Experiment 1; P < 0.05, Experiment 2). Characteristics measured, including age, weight, scrotal circumference, and reaction time, were all unrelated to bulls serving capacity in both experiments, as well as to breeding soudness examination scores for bulls in Experiment 1. There was a dramatic impact of sexual experience school on subsequent serving capacity, since 85% of sexual experience school bulls moved into the medium or high serving capacity category at the second serving capacity test. It is concluded that serving capacity can successfully be evaluated in yearling beef bulls under field conditions, that sire has a profound impact on bulls serving capacity, and that providing sexual experience to low serving capacity bulls can improve their serving capacity.

Journal Article↗

Effects of prepartum energy intake on steroids during late gestation and on cow and calf performance.

At 50 d prior to predicted calving, 37 multiparous Angus cows were grouped by sire of mating, age and weight of cow and placed on either a high energy (HE, n = 19) diet or a moderate energy (ME, n = 18) diet. Objectives were to determine the effect of prepartum nutrition on: prepartum serum concentrations of estrone (E1), estrone sulfate (E1SO4) and progesterone (P4); pre- and postpartum cow body weight changes; calf birth weight and cow and calf postpartum performance. The ME cows were group-fed Coastal bermudagrass hay ad libitum and dormant pasture; HE cows were group-fed 2.7 kg ground corn X head-1 X d-1 in addition to the ME treatment. Both groups were combined and fed identically after calving. Cows fed HE were heavier (P less than .01) than cows fed ME at d 10 prepartum and their calves were heavier (P less than .05) at birth and weaning than calves from cows fed ME. Serum E1 concentrations were not significantly different between groups, but serum E1SO4 was higher (P less than .01) at d 10 prepartum in ME cows compared with HE cows. Serum P4 concentrations of ME cows were higher (P less than .05) than those of HE cows. Cow body weights were greater (P less than .01) for the HE group than for the ME group during the first 6 mo postpartum. Cow rebreeding performance was identical for both groups.

Animals↗

The availability of nitroglycerin from parenteral solutions.

The availability of nitroglycerin from solution infused from Viaflex plastic infusion bags or glass infusion bottles through Buretrol plastic giving sets has been examined. Each of the individual components of the infusion bag/giving set system (i.e. infusion bag, burette and infusion tubing) sorbed nitroglycerin to a significant extent. It was found that the event and rate of nitroglycerin disappearance from solutions stored in each of the components were in the rank order: tubing greater than burette greater than infusion bag. The disappearance kinetics of nitroglycerin from solutions stored in each component was more accurately described by a 'diffusion' model than by the 'two compartment kinetic' model reported previously. The dimensions of the components and the volume of solution used were determinants of the rate and extent of nitroglycerin disappearance. In simulated infusions of nitroglycerin through plastic infusion bag (or glass bottle)/giving set system the flow rate of solution through the plastic infusion tubing affected the concentration of nitroglycerin in the effluent and the extent of sorption by the components of the infusion delivery system. The loss of nitroglycerin in these studies could be accounted for solely by the sorption of nitroglycerin by the plastic components of the infusion bag/giving set system.

Biological Availability↗

The prolonged pressor response to renin in the nephrectomized rat.

Angiotension I dose-response curves and renin clearances were studied in nephrectomized and paired sham-nephrectomized control rats under pentobarbital anesthesia. Both threshold and slope of the angiotensin dose-response curves were decreased 22 hours after nephrectomy. In addition, the ratio of renin clearance (determined during renin infusions) in the 22-hour-nephrectomized rat to that in paired 22-hour sham-nephrectomized controls was 0.50 +/- 0.03 (mean +/- SEM, P less than 0.001, n = 12 pairs). The finding of reduced renin clearance was confirmed by an indirect assessment of "effective renin clearance" based on a comparison of the blood pressure decline after renin injections with angiotensin I dose-response curves in the same rat. Overall, approximately half of the 50% fall in renin clearance could be accounted for by an immediate effect of removal of the kidney on renin clearance. This role of the kidney in renin clearance was confirmed by the finding of a renal venous-arterial renin ratio of 0.9 +/- 0.03 (P less than 0.005) during renin infusion in normal rats. It is concluded that both changes in the angiotensin I dose-response curve and decrease in plasma renin clearance contribute to the postnephrectomy prolongation of the renin pressor response in the rat.

Angiotensin I↗

Loss of nitroglycerin from intravenous infusion sets.

During initial studies with nitroglycerin infusion in patients with acute myocardial infarction, higher doses than previously reported were required to achieve the desired haemodynamic effect. A flow-rate-dependent loss of drug from the plastic infusion set was demonstrated during simulated infusion. This loss was considerably reduced when nitroglycerin was infused from glass syringes through high-density polyethylene tubing.

Acute Disease↗

An inactive higher-molecular-weight renin in normal subjects and hypertensive patients.

Inactive renin which can be converted to an enzymologically active form by acidification to pH 3-3 by dialysis was found in normal subjects and in patients with untreated essential hypertension. The molecular weight of this inactive renin (43 000) is 2000 +/- 900 (S.E.M.) daltons higher (p less than 0.05) than that of naturally occurring active renin and the two forms of renin could be clearly separated by ion-exchange chromatography with diethylaminoethyl-"Sepharose'. Patients with low-renin essential hypertension had proportionately larger amounts of inactive renin than usual, so that the total renin in these patients approached the normal range. Inactive renin seems likely to be a form in which the enzyme is secreted since in a patient with renal-artery stenosis its concentration was greater in the renal-vein blood coming from the affected kidney.

Chromatography, Gel↗

An investigation of the prolonged pressor response to renin in the nephrectomized rat.

1. In an investigation of the prolonged pressor response to renin that develops after nephrectomy, angiotensin I dose-response curves and rat renin clearances were studied in nephrectomized rats and paired sham-nephrectomized control animals under pentobarbitone anaesthesia. 2. Both threshold and slope of the angiotensin I dose-response curves were decreased at 15-27 h after nephrectomy. 3. The ratio of renin clearance (determined during renin infusions) in the nephrectomized rat to that in the paired sham-nephrectomized control animals was 0-49+/-0-03 (SEM), P less than 0-001 (n = 12 pairs). 4. Both factors contribute towards the prolongation of the blood pressure increase after intravenously administered renin in the nephrectomized animal.

Angiotensin II↗

Essential hypertension--the starting point for improved drug treatment.

Hypertension is a common disease and plays an important role as a potentially remediable contributor to cardiovascular causes of death in the community. In moderate to severe hypertension recent treatment has improved morbidity and mortality substantially, but it is disappointing that despite this myocardial infarction still stands as an important cause of death. In this regard it is encouraging that beta adrenergic blockade may be useful not only in lowering blood pressure, but also possibly in reducing independently the risk of myocardial infarction and/or sudden death in some patients. In mild hypertension the number of patients is large and the possible beneficial effect of treatment less well-established, so that there is a clear need for further research in order to define patients at relatively high risk in this group.

Adrenergic beta-Antagonists↗

The pharmacokinetic characteristics of beta-receptor antagonists in man--similarities and differences of clinical relevance.

The aliphatic partial structure common to the beta-receptor antagonists leads to similar products of their biotransformation. The main qualitative and quantitative differences of the metabolism of the compounds of this class, however, rest in the nature of their aromatic or heterocyclic substituents. The physico-chemical properties of the beta-blockers appear to be predominantly responsible for the extent of metabolic degradation and for the distribution in the body, especially for the binding to proteins. As a consequence of their different biological disposition the clinically relevant systemic bioavailabilities of the various beta-blockers from oral doses differ drastically. Practolol maintains an extreme position among all other compounds: It is most hydrophilic, it is not bound to proteins, it is metabolized least, but cleared renally in unchanged form to 85% of the dose. Despite its extremely high systemic bioavailability, relatively high daily doses were required for therapy. The receptor sensitivity for practolol has been rated 2 to 3 powers of 1- lower than of propranolol. Comparative pharmacokinetic assessment of beta-receptor antagonists requires quantitative analytical data in clinically representative groups of patients. This has been demonstrated by respective studies with oxprenolol. The intra- and inter-individual systemic bioavailability, the differential analysis of plasma and erythrocytes, the multiexponential elimination kinetics, and their possible dependence on the dose have been studied as clinically relevant pharmacokinetic characteristics. The continuing attempt of the pharmaceutical industry to optimize the properties of beta-blockers also has taken advantage of the slow release principle in oral dosage forms as shown by the example of oxprenolol. The beta-receptor antagonists belong to one of the youngest classes of pharmaceuticals. Pharmacokinetic and metabolic data for the different representatives of this class have been generated in different laboratories with different approaches and different techniques. Therefore, full comparative documentation is still incomplete.

Adrenergic beta-Antagonists↗

Effect of the angiotensin II blocker 1-Sar-8-Ala-angiotensin II on renal artery clip hypertension in the rat.

Twenty-four conscious male Wistar rats with hypertension induced by left renal artery clipping (two-kidney hypertension) were infused intravenously with 1-Sar-8-Ala-angiotensin II a competitive angiotensin II antagonist. The spectrum of responses was wide, ranging from a mild elevation in blood pressure to a marked fall in blood pressure, despite effective and specific angiotensin blockade in all cases. The change in blood pressure during 1-Sar-8-Ala-AII infusion activity showed a significant correlation with the level of plasma renin prevailing immediately before the infusion (r = - 0.78, P less than 0.01) but not with the prevailing blood urea level (r = 0.27, 0.1 greater than P greater than 0.05), the drgree of hypertension (r = 0.42, 0.1 greater than P greater than 0.05), or the time since clipping (r = 0.02, P greater than 0.05). There was no significant correlation between the degree of hypertension and the plasma renin activity (r = 0.42, 0.1 greater than P greater than 0.05). In rats with blood pressure drops greater than 20 mm Hg in response to 1-Sar-8-Ala-AII, the final blood pressure level was still above the normotensive range. Excision of the clipped kidney reduced blood pressure to normal or to near normal within 24 hours in all of the rats tested. It is concluded that the degree of dependence of renal hypertension on the renin-angiotensin system is directly related to the increase in circulating angiotensin itself and not to an increase in sensitivity to angiotensin. Other factors appear to be involved in renal clip hypertension in addition to circulating renin and angiotensin, especially when the measured activity of plasma renin is normal.

Angiotensin II↗