Search PubMed⌕ Search

Biomedical subjects

R G Evans

Publications and source records attributed to R G Evans.

At least 55 records · Page 3Linked to original sources
PubMed1999

Renal hemodynamic responses to intrarenal infusion of ligands for the putative angiotensin IV receptor in anesthetized rats.

Angiotensin IV, a hexapeptide fragment (3-8) of angiotensin II metabolism, has been reported to produce vasodilatation within the renal vasculature by activation of the putative AT4 receptor. However, there are conflicting findings, with previous in vivo studies providing evidence for and against a renal vasodilator action of angiotensin IV. In this study, the renal hemodynamic responses to activation of the putative AT4 receptor were studied in anesthetized rats by left renal arterial infusion of two endogenous ligands, angiotensin IV and LVV-hemorphin-7. Angiotensin IV (10, 100, and 1,000 pmol/min) infusion caused dose-dependent reductions in blood flow to the infused kidney, which were abolished by pretreatment with losartan. In respect to this effect, angiotensin IV was approximately 300-fold less potent than angiotensin II. There were no significant effects of angiotensin IV on mean arterial pressure, heart rate, or blood flow to the noninfused kidney. Intrarenal infusion of LVV-hemorphin-7 (10, 100, and 1,000 pmol/min) had no significant effect on renal blood flow in the infused and noninfused kidneys, or on mean arterial pressure or heart rate. These results provide no evidence for a renal vasodilatory action of angiotensin IV or LVV-hemorphin-7. On the contrary, intrarenal angiotensin IV infusion produced vasoconstriction of the renal vasculature, mediated by activation of AT1 receptors. These observations provide evidence against a vasodilatory role of putative AT4 receptors in the rat kidney.

Anesthesia↗
PubMed1999

Renal medullary interstitial infusion of norepinephrine in anesthetized rabbits: methodological considerations.

We tested methods for delivery of drugs to the renal medulla of anesthetized rabbits. Outer medullary infusion (OMI) of norepinephrine (300 ng. kg(-1). min(-1)), using acutely or chronically positioned catheters, reduced both cortical (CBF; 15%) and medullary perfusion (MBF; 23-31%). Inner medullary infusion (IMI) did not affect renal hemodynamics, whereas intravenous infusion reduced CBF (15%) without changes in MBF. During OMI of [(3)H]norepinephrine, much of the radiolabel (approximately 40% with chronically positioned catheters) spilled over systemically. Nevertheless, autoradiographic analysis showed the concentration of radiolabel was about fourfold greater in the infused medulla than the cortex. In contrast, during IMI, only approximately 5% of the infused radiolabel spilled over into the systemic circulation and approximately 64% was excreted by the infused kidney. The resultant intrarenal levels of radiolabel were considerably less with IMI compared with OMI. In rabbits, OMI therefore provides a useful method for targeting agents to the renal medulla, but given the considerable systemic spillover with OMI, its utility is probably limited to substances that are rapidly degraded in vivo.

Anesthesia↗
PubMed1999

Mortality rates after cataract extraction.

Senile cataract may be a marker of generalized tissue aging. We examined this hypothesis using population-based linked health data. We hypothesized that any such association would diminish with increased use of cataract surgery. Mortality rates of those 50-95 years of age undergoing cataract surgery in British Columbia during either 1985 or 1989 were compared with the provincial population of comparable age who did not undergo cataract surgery during the study period. The 1985 cohort included 8,262 patients undergoing surgery and a comparison population of 804,303, and the 1989 cohort included 11,952 patients and a comparison population of 839,393. Using Cox regression, for the 1985 cohort, the hazard ratios for dying during follow-up were 3.2 for males 50-54.9 years of age [95% confidence limits (CL) = 2.0, 5.0] and 3.3 for females (95% CL = 1.9, 5.7). Hazard ratios for older age groups decreased with age. We also fit an additive risk model that produced excess mortalities that were less age dependent. In the 1985 analysis, these ranged from +7.1 per 1,000 (95% CL = +0.44, +13.76) to +20.3 (95% CL = +13.24, +27.36) for males and -17.5 (95% CL = -28.28, -6.72) to +2.0 (95% CL = -2.12, +6.12) for females. Findings for the 1989 analyses were similar, indicating that the association between cataracts and generalized aging remained constant despite a large increase in the use of cataract surgery.

Age Distribution↗
PubMed1998

Do different levels and patterns of sympathetic activation all provoke renal vasoconstriction?

Renal sympathetic nerve activity (RSNA) is postulated to influence renal function in selective ways with changes in renal hemodynamics only occurring during high stimulus intensities. The aim of this study was to determine the renal blood flow (RBF) response to a number of stimuli designed to increase RSNA by a modest amount and assess the possibility that different afferent stimuli produce differential levels of vasoconstriction by differentially altering the pattern of RSNA. Experiments were performed in eight conscious rabbits subjected to 20 min periods of three stimuli noise stress, air jet stress or hypoxia (10% O2). RSNA was significantly increased 12 +/- 4, 31 +/- 8 and 14 +/- 5% (means of 20 min periods +/- SEM) and these effects were mirrored in the significant changes in RBF over the period of each stimuli with mean reductions of 8 +/- 1, 10 +/- 3 and 8 +/- 4% during noise, air jet stress and hypoxia respectively. Changes in plasma renin activity did not occur without changes in RBF. With regard to the pattern of RSNA discharges, hypoxia selectively increased the amplitude (number of recruited nerves) while noise and air jet stress increased both the amplitude and frequency of discharges. The role of the renal nerves in these responses and in providing a tonic level of vasoconstriction within the kidney, was demonstrated in experiments on a group of eight renal denervated animals. The renal denervated rabbits had greater resting RBF than the intact rabbits (54 +/- 1 denervated vs. 38 +/- 1 ml min(-1) intact), and RBF was not altered by any of the afferent stimuli. We conclude that small changes in RSNA, irrespective of the stimulus, modulate renal blood flow.

Acoustic Stimulation↗
PubMed1998

Socioeconomic status, mortality, and the development of cataract at a young age.

It has been hypothesized that senile cataract may serve as a marker for generalised tissue aging, since structural changes occurring in the proteins of the lens during cataract formation are similar to those which occur elsewhere as part of the aging process. An earlier analysis we carried out to test this hypothesis revealed a strong age-dependent relationship between undergoing cataract surgery and subsequent mortality. Relative risks for dying over 9 yr of follow-up were particularly increased for individuals who had developed cataract requiring operation between the ages of 50-65. This finding prompted us to test the hypothesis that younger patients undergoing surgery for cataract (those in which surgery was undertaken at 50-65 yr of age) would tend disproportionately to be resident in areas of generally lower socioeconomic status. A population-based linked health data resource containing data on all hospital separations in the province of British Columbia was used to examine this hypothesis. Linkage to Canadian census data was used to assign a socioeconomic decile to the area of residence for all individuals in British Columbia who either did, or did not, undergo cataract surgery over a 3 yr period, and were aged 50-95. Relative to those who resided in the highest socioeconomic areas, odds ratios for undergoing cataract surgery between 50 and 65 yr of age were significantly greater than 1 for the four lowest socioeconomic deciles. This association was observed despite a conservative bias in our setting that favoured those of higher socioeconomic status tending to receive earlier treatment. The results of this ecologic study prompt consideration of whether factors which have the dual attributes of being correlates of socioeconomic status and implicated in the development of cataract may play a role in mediating the processes involved in the well known association of socioeconomic status and mortality.

Age Factors↗
PubMed1998

Effects of intrarenal infusion of 17-octadecynoic acid on renal antihypertensive mechanisms in anesthetized rabbits.

To characterize the role of cytochrome P450 metabolism of fatty acids in the renal response to increased renal perfusion pressure, we tested the effects of renal arterial infusion of 17-octadecynoic acid (17-ODYA, 450 nmol/min) on renal and systemic hemodynamic, and renal excretory responses to step-wise increases in renal perfusion pressure (RPP) in anesthetized rabbits, using an extracorporeal circuit for renal autoperfusion. Inhibition of cytochrome P450-dependent fatty acid metabolism was estimated by comparing the metabolism of arachidonic acid in microsomes prepared from the kidneys of control and 17-ODYA-treated animals. Step-wise increases in RPP decreased mean arterial pressure, which previous studies have indicated is attributable to the release of a depressor hormone from the renal medulla. Elevations in RPP also increased renal blood flow and glomerular filtration rate, and the absolute and fractional excretions of urine and sodium. Intrarenal infusion of 17-ODYA reduced the metabolism of arachidonic acid to 20-hydroxyeicosatetraenoic acid by 41%, but it did not significantly influence the responses to increased renal perfusion pressure. We conclude that either the responses elicited by increased renal perfusion pressure in anesthetized rabbits do not depend on cytochrome P450-dependent fatty acid metabolism, or that cytochrome P450 activity must be inhibited by more than was achieved in the present study (41%), before functional effects on the response to increased renal perfusion pressure are observed.

Anesthesia↗
PubMed1998

Renal haemodynamic effects of endothelin-1 and the ETA/ETB antagonist TAK-044 in anaesthetized rabbits.

OBJECTIVE: The aim of this study was to test the effects of exogenous endothelin-1 (ET-1) on regional kidney blood flow and renal function, and the renal haemodynamic effects of endogenous ET, in anaesthetized rabbits. METHODS: ET-1 was infused into the left renal artery at 2 ng/kg/min for 30 min, then at 1 ng/kg/min. Cumulative doses of TAK-044 (0.1-3 mg/kg, i.v.) or its vehicle were given at 30-min intervals. In other rabbits, an extracorporeal circuit was established to adjust renal arterial pressure (RAP) independently of systemic arterial pressure (MAP). RAP was set at 65 mmHg, and either TAK-044 (3 mg/kg, i.v.) or its vehicle was administered. RESULTS: In the infused kidney ET-1 (2 ng/kg/min) reduced renal blood flow (RBFprobe; 52+/-8%), cortical perfusion (37+/-7%), glomerular filtration rate (GFR; 49+/-8%), urine flow (47+/-14%) and sodium excretion (49+/-13%), but not medullary perfusion (5+/-6%). No effects of ET-1 on MAP or on the contralateral kidney were observed. TAK-044 dose-dependently reversed the effects of ET-1 on RBFprobe and cortical perfusion. TAK-044 also reduced MAP (by up to 11+/-3%) and increased effective renal blood flow in the contralateral kidney (by up to 46+/-27%). In the extracorporeal circuit model, TAK-044 decreased MAP by 12+/-2% and RAP by 10+/-3%, and increased RBF by 9+/-3%. CONCLUSION: Exogenous ET-1 reduces cortical more than medullary perfusion, and reduces GFR without affecting net tubular sodium and fluid reabsorption. TAK-044 antagonizes local renal vascular responses to ET-1. Endogenous ETs appear to contribute markedly to resting renal vasomotor tone and MAP.

Animals↗
PubMed1998

Effects of the vasopressin V1 agonist [Phe2,Ile3,Orn8]] vasopressin on regional kidney perfusion and renal excretory function in anesthetized rabbits.

To test whether renal V1-receptors selectively influence blood flow in the renal medulla, we compared the effects of infusion of [Phe2,Ile3,Orn8]vasopressin (3-30 ng/kg/min) by the intravenous, renal arterial, and renal medullary interstitial routes in anesthetized rabbits. Intravenous [Phe2,Ile3,Orn8]vasopressin (30 ng/kg/min) reduced renal medullary perfusion (MBF) by 36 +/- 5% but did not significantly affect cortical perfusion (CBF). MBF was also reduced with the renal arterial (35 +/- 5%) and renal medullary interstitial (40 +/- 7%) routes but, in contrast to the intravenous infusion, CBF was also reduced, by 21 +/- 3% and 15 +/- 3%, respectively. Urine flow and sodium excretion were increased by [Phe2,Ile3,Orn8]vasopressin, and with direct intrarenal administration, this effect was similar for both the infused (left) and noninfused (right) kidneys. After a 20-min renal medullary interstitial infusion of [3H]norepinephrine, radiolabel concentration was approximately fivefold greater in the left medulla than in the left cortex. We conclude that [Phe2,Ile3,Orn8]vasopressin acts on V1-receptors to alter regional kidney blood flow and tubular salt and water handling. The V1-receptors involved are almost certainly within the kidney itself, but given the contrasting effects of the different infusion routes on MBF and CBF, we cannot exclude the possibility that some of the observed effects of [Phe2,Ile3,Orn8]vasopressin are mediated by activation of extra-renal V1-receptors.

Angiotensin II↗
PubMed1998

Contribution of renal nerves to renal blood flow variability during hemorrhage.

We have examined the role of the renal sympathetic nerves in the renal blood flow (RBF) response to hemorrhage in seven conscious rabbits. Hemorrhage was produced by blood withdrawal at 1.35 ml.min(-1).kg-1 for 20 min while RBF and renal sympathetic nerve activity (RSNA) were simultaneously measured. Hemorrhage was associated with a gradual increase in RSNA and decrease in RBF from the 4th min. In seven denervated animals, the resting RBF before hemorrhage was significantly greater (48 +/- 1 vs. 31 +/- 1 ml/min intact), and the decrease in RBF did not occur until arterial pressure also began to fall (8th min); however, the overall percentage change in RBF by 20 min of blood withdrawal was similar. Spectral analysis was used to identify the nature of oscillations in each variable. Before hemorrhage, a rhythm at approximately 0.3 Hz was observed in RSNA, although not in RBF, whose spectrogram was composed mostly of lower-frequency (< 0.25 Hz) components. The denervated group of rabbits had similar frequency spectrums for RBF before hemorrhage. RSNA played a role in dampening the effect of oscillations in arterial pressure on RBF as the transfer gain between mean arterial pressure (MAP) and RBF for frequencies > 0.25 Hz was significantly less in intact than denervated rabbits (0.83 +/- 0.12 vs. 1.19 +/- 0.10 ml.min(-1).mmHg-1). Furthermore, the coherence between MAP and RBF was also significantly higher in denervated rabbits, suggesting tighter coupling between the two variables in the absence of RSNA. Before the onset of significant decreases in arterial pressure (up to 10 min), there was an increase in the strength of oscillations centered around 0.3 Hz in RSNA. These wer accompanied by increases in the spectral power of RBF at the same frequency. Arterial pressure fell in both groups of animals, the dominant rhythm to emerge in RBF was centered between 0.15 and 0.20 Hz and was present in intact and denervated rabbits. It is speculated that this myogenic in origin. We conclude that RSNA can induce oscillations in RBF at 0.3 Hz, plays a significant role in altering the effect of oscillations in arterial pressure on RBF, and mediates a proportion of renal vasoconstriction during hemorrhage in conscious rabbits.

Animals↗
PubMed1998

Effects of renal medullary infusion of a vasopressin V1 agonist on renal antihypertensive mechanisms in rabbits.

The factors responsible for the development of hypertension during chronic activation of intrarenal V1 receptors are unknown. We therefore tested whether medullary interstitial infusion of the selective V1-receptor agonist [Phe2,Ile3,Orn8]vasopressin (V1 agonist) influences renal antihypertensive mechanisms initiated by increased renal perfusion pressure (RPP). In intact anesthetized rabbits, the V1 agonist (10 ng . kg-1 . min-1) reduced medullary perfusion by 36 +/- 7%, whereas cortical perfusion was reduced by only 14 +/- 2%. An extracorporeal circuit was used to increase RPP in a stepwise manner from 65 to 85, 110, 130, and 160 mmHg for consecutive 20-min periods. Increased RPP reduced mean arterial pressure by 35 +/- 8% in vehicle-treated rabbits, but by only 10 +/- 3% in V1 agonist-treated rabbits. Simultaneously, pressure-diuresis-natriuresis was induced; urine flow and sodium excretion increased similarly in the two groups of rabbits, but hematocrit did not change. We suggest that the depressor response to increased RPP is mainly due to release of a putative renal medullary depressor hormone (RMDH). Suppression of the release and/or actions of RMDH may therefore contribute to the hypertensive effect of chronic V1 receptor activation.

Analysis of Variance↗
PubMed1997

CHOP-based chemotherapy is as effective as alternating PEEC/CHOP chemotherapy in a randomised trial in high-grade non-Hodgkin's lymphoma. Scotland and Newcastle Lymphoma Group.

The aim of this study was to test whether survival for patients with high-grade non-Hodgkin's lymphoma (NHL) can be improved with a non-cross-resistant regimen as compared to a CHOP-based regimen. This is a multicentre study comprising 325 adult patients, median age 58 years, with high-grade non-Hodgkin's lymphoma: patients of any age and performance status were eligible provided they were able to receive the drugs in the regimens. Patients were randomised to either B-CHOP-M (bleomycin, cyclophosphamide, doxorubicin, vincristine, prednisolone and methotrexate) or PEEC-M (methylprednisolone, vindesine, etoposide, chlorambucil and methotrexate) alternating with B-CHOP-M. At a median follow-up of 9 years, there was no significant difference in overall survival or disease-free survival between the two arms. Toxicities for the two regimens were equivalent. This study confirms that for relatively unselected patients with high-grade non-Hodgkin's lymphoma, an alternating multidrug regimen does not improve upon the results obtained with B-CHOP-M.

Adult↗
PubMed1997

Chronic renal blood flow measurement in dogs by transit-time ultrasound flowmetry.

To test the validity of transit-time ultrasound flowmetry for chronic measurement of renal blood flow in dogs, we compared this method with the renal clearance of para-aminohippuric acid (CPAH) (corrected for hematocrit), and with direct volumetric measurements. When flow-probes were implanted without silastic sheeting to stabilize the implant, there was significant disparity between the (within-dog) mean levels of renal blood flow estimated by flow-probe and CPAH. In contrast, when the flow-probe implants were stabilized with silicone sheeting, there was close agreement in each dog between the flow rates measured by the two methods. When flow-probes were calibrated volumetrically in situ, there was a close linear relationship between flow derived from the flow-probe and that measured volumetrically (r = 0.98 +/- 0.02). We conclude that valid, chronic measurement of renal blood flow in dogs can be achieved using transit-time ultrasound flowmetry, provided the implant is stabilized with silicone sheeting.

Animals↗
PubMed1997

Evidence for decreased structurally determined preglomerular resistance in the young spontaneously hypertensive rat after 4 weeks of renal denervation.

OBJECTIVES: To study the effects of denervation of the kidney on renal vascular resistance at maximal dilatation and renal function during the development of hypertension in the spontaneously hypertensive rat (SHR). METHODS: SHR aged 6 weeks were subjected to left renal denervation or a sham-operation (n = 18 denervated, n = 13 sham). When they were aged 10 weeks, pairs of denervated and sham-operated left kidneys were perfused with 2% dextran in Tyrode's solution and pressure-flow and pressure-glomerular filtration rate (GFR) relationships at maximal vasodilation were established. The awake mean arterial blood pressure, in-vivo renal function and renal noradrenaline content were also measured. RESULTS: There were no significant differences between the pressure-flow relationships for denervated and sham-operated kidneys. However, there was a marked, parallel, shift leftwards in the pressure-GFR relationship (P < 0.001). Thus, the denervated kidneys commenced filtering at a lower threshold perfusion pressure than did the sham-operated ones. In-vivo renal plasma flow and GFR were significantly greater in the denervated left kidneys of SHR than they were in the contralateral kidneys. The noradrenaline content in denervated kidneys was 5 +/- 3% of that in innervated kidneys. The awake mean arterial pressure was 135 +/- 1 and 138 +/- 2 mmHg in the denervated and sham-operated groups respectively. CONCLUSION: Denervation of the kidney of SHR aged 6 weeks of age altered the pressure-GFR but not the pressure-flow relationship for these rats 4 weeks later. The results are compatible with there having been an increase in average preglomerular and a decrease in post-glomerular vessel lumen diameters. These changes suggest that the renal nerves affect the structural development of the renal vasculature in SHR.

Animals↗
PubMed1997

Chronic intrarenal infusion of low-dose angiotensin II in dogs increases arterial pressure without impairment of renal function.

1. To determine whether chronic angiotensin II (AngII) infusion into the renal artery, at a dose which increases systemic arterial pressure, reduces glomerular filtration rate (GFR) and renal blood flow, AngII was infused at 0.5 ng/kg per min into the renal artery or intravenously in chronically instrumented dogs for 1 month. 2. Mean arterial pressure (MAP) rose significantly (P < 0.05) during the infusion of AngII into the renal artery (+7 +/- 2 mmHg on days 26-30). There were no significant changes in GFR or renal blood flow. When the same dose of AngII was infused intravenously, MAP did not change significantly (-2 +/- 2 mmHg) and there were no significant changes in GFR or in renal blood flow. 3. We conclude that AngII infused into the renal artery for 1 month, at a dose which was initially subpressor, causes a rise in arterial pressure that is not associated with impairment of renal function.

Angiotensin II↗
PubMed1997

Renal effects of rilmenidine in volume-loaded anaesthetized dogs.

1. In anaesthetized, fluid expanded rats rilmenidine has diuretic and natriuretic effects. There is strong evidence that the natriuresis is mediated by putative imidazoline receptors. In contrast, in conscious euvolaemic dogs rilmenidine has a diuretic effect that is entirely attributable to activation of alpha 2-adrenoceptors, but no natriuretic effect. To determine whether the effects of rilmenidine are truly species dependent, or merely dependent upon the influences of anaesthesia and volume status, we tested the effects of rilmenidine in pentobarbitone anaesthetized, volume-loaded dogs. 2. The effects of rilmenidine in anaesthetized, volume-loaded dogs were similar to those found in conscious euvolaemic dogs. Compared with vehicle treatment, levels of glomerular filtration rate, urine flow and haematocrit were increased following rilmenidine treatment. No effect of rilmenidine on sodium excretion was observed. 3. We conclude that the renal responses to rilmenidine in dogs are largely unaffected by anaesthesia and plasma volume status. In particular, the natriuretic effect seen in rats was not observed. We conclude that putative imidazoline receptors do not have a major influence on sodium excretion in dogs.

Anesthesia↗
PubMed1997

Systemic hemodynamic responses to chronic angiotensin II infusion into the renal artery of dogs.

Chronic intrarenal infusion of angiotensin II (0.5 ng.kg-1.min-1) in dogs increases arterial pressure. In the present study we determined whether this was associated with changes in cardiac output or in total peripheral resistance. Mean arterial pressure did not change initially but was significantly increased over days 14-28 of the infusion period (+6 +/- 2 mmHg), as was total peripheral resistance (+4 +/- 2 mmHg.min.l-1). Neither cardiac output, renal blood flow, nor glomerular filtration rate was significantly changed over this period. To determine the influence of the autonomic nervous system on the developing hypertension, periodic acute autonomic ganglion blockade was performed. Before angiotensin II infusion ganglion blockade reduced total peripheral resistance and increased cardiac output, and this effect was similar across the 4 wk of angiotensin II infusion. Systemic hemodynamics were not affected by intravenous angiotensin II infusion (0.5 ng.kg-1.min-1). Thus intrarenal infusion of low-dose angiotensin II produced a chronic increase in arterial pressure due to an action within the kidney. The hypertension was associated with increased total peripheral resistance but not with marked changes in cardiac output or renal function or in the influence of the autonomic nervous system on systemic hemodynamics.

Angiotensin II↗