Biomedical subjects

K M Denton

Publications and source records attributed to K M Denton.

At least 19 recordsLinked to original sources

PubMed2006

Sex differences in postnatal growth and renal development in offspring of rabbit mothers with chronic secondary hypertension.

Previously, we demonstrated that adult blood pressure was increased in offspring of rabbit mothers with chronic secondary renal hypertension. Our study identified sex-specific differences in the programming of hypertension, with female, not male, offspring, having increased blood pressure at 30 wk of age. The aim of this study was to characterize the maternal hypertension during pregnancy to determine potential programming stimuli. Further, we examined the impact of chronic maternal hypertension on offspring birth weight, nephron number, and renal noradrenaline content (as an index of renal innervation density). Three groups of mothers and their offspring were studied: two-kidney, one-wrap (2K-1W, n = 9 mothers) hypertensive, two-kidney, two-wrap (2K-2W, n = 8) hypertensive, and a sham-operated group (n = 9). Mean arterial blood pressure was increased by approximately 20 mmHg throughout pregnancy in both hypertensive groups compared with sham mothers (P(G) < 0.001). Plasma renin activity (PRA; P(G) < 0.05) and aldosterone (P(G) < 0.05) levels were increased during gestation in the 2K-1W, but not the 2K-2W mothers. Birth weight was increased by approximately 20% in offspring of both groups of hypertensive mothers (P(T) < 0.001), though this was associated with a reduction in litter size. Renal noradrenaline content was increased ( approximately 40%, P < 0.05) at 5 wk of age in female 2K-1W offspring compared with sham offspring. Glomerular number was not reduced in female offspring of either group of hypertensive mothers; however, glomerular tuft volume was reduced in female 2K-2W offspring (P < 0.05), indicative of a reduction in glomerular filtration surface area. In conclusion, the two models of renal hypertension produced differential effects on the offspring. The impact of a stimulated maternal renin-angiotensin system in the 2K-1W model of hypertension may influence development of the renal sympathetic nerves and contribute to programming of adult hypertension.

Aldosterone↗

PubMed2006

A developmental nephron deficit in rats is associated with increased susceptibility to a secondary renal injury due to advanced glycation end-products.

AIMS/HYPOTHESIS: The aim of this study was to investigate the effects of a secondary renal insult, due to chronic infusion of AGEs on renal function, and on early pathological markers in rats with a developmental nephron deficit. METHODS: Female Wistar-Kyoto rats were fed a low-protein diet (LPD; 8.7% casein) or a normal-protein diet (NPD; 20% casein) during pregnancy and lactation. Nephron number was estimated in 4-week-old female offspring. Male offspring were allowed to grow to 20 weeks of age, when AGEs derived from BSA (AGE-BSA) or BSA was infused subcutaneously (20 mg kg(-1) day(-1)) for 4 weeks. At 24 weeks, blood pressure, renal function and circulating and renal AGEs were assessed. Real-time PCR was used to investigate early molecular markers of renal pathology. RESULTS: As expected, maternal protein restriction led to reduced nephron endowment in LPD offspring. This alone did not affect blood pressure or lead to hyperfiltration in adulthood. However, when coupled with the secondary renal insult, the expression of the genes encoding transforming growth factor-beta(1) and procollagen III was significantly upregulated in the kidneys. In addition, there was renal accumulation of AGEs in LPD offspring, and this was exacerbated by AGE infusion. CONCLUSIONS/INTERPRETATION: Our results demonstrate that the adult kidney with a reduced nephron endowment is more vulnerable to secondary renal insult from AGE-BSA. Since AGE formation is markedly elevated with hyperglycaemia, our findings suggest that a developmental or acquired deficit may render the kidney susceptible to diabetic renal disease.

Aging↗

PubMed2006

Lack of contribution of P2X receptors to neurally mediated vasoconstriction in the rabbit kidney in vivo.

AIM: The contribution of adenosine triphosphate (ATP) to the neural control of regional renal perfusion in vivo remains unknown. We therefore examined whether P2X receptors mediate renal vascular responses to electrical stimulation of the renal nerves (RNS) in pentobarbitone anaesthetized rabbits. METHODS: Responses to RNS were tested before and during renal arterial infusion of alpha,beta-methylene ATP (alpha,beta-mATP, 7-56 microg kg(-1) min(-1)) to desensitize P2X1 receptors. RNS consisted of 3 min trains at graded frequencies and short trains of RNS (4-32 pulses). RESULTS: Three-minute trains of RNS reduced renal blood flow (RBF), cortical laser Doppler flux (CLDF), and medullary LDF (MLDF) by -90 +/- 3%, -89 +/- 3% and -31 +/- 11%, respectively, at 4 Hz. MLDF was reduced less than CLDF or RBF. During short train RNS, RBF, CLDF and MLDF were reduced by -22 +/- 2%, -15 +/- 2% and -12 +/- 2%, respectively, for 32 s at 1 Hz. CLDF and MLDF were reduced to a similar extent. Infusion of alpha,beta-mATP induced transient reductions in RBF, CLDF and MLDF, but within 5 min these variables had recovered to control levels. Vascular responses to RNS were not significantly altered by alpha,beta-mATP treatment. CONCLUSIONS: In the rabbit kidney in vivo, alpha,beta-mATP-sensitive receptors mediate vasoconstriction and reduce perfusion in both cortical and medullary vascular beds. However, these receptors do not mediate neurally induced reductions in renal perfusion.

Animals↗

PubMed2001

Metalloendopeptidases EC 3.4.24.15 and EC 3.4.24.16 and bradykinin B2 receptors do not play important roles in renal wrap hypertension in rabbits.

1. The aim of the present study was to determine the effects of the metalloendopeptidase (EP) 24.15 and 24.16 inhibitor N-[1-(R,S)-carboxy-3-phenylpropyl]-Ala-Aib-Tyr-p-aminobenzoate (JA-2) on haemodynamics and renal function in conscious rabbits with two-kidney, two-wrapped hypertension. We have also examined the role of endogenous bradykinin in the maintenance phase of this form of renovascular hypertension and whether inhibition of bradykinin degradation contributes to any potential effects of JA-2. 2. In two preliminary operations, rabbits were equipped with transit-time ultrasound flow probes for measuring cardiac output (CO) and renal blood flow (RBF) and had both kidneys wrapped in cellophane. Starting 4 weeks after the last operation, rabbits underwent four studies (3-5 days apart), during which they were treated with combinations of the bradykinin B2 receptor antagonist icatibant or its vehicle (1 mL/kg bodyweight 0.9% w/v NaCl) and JA-2 or its vehicle (1 mL/kg of a 5% w/v 2-hydroxypropyl-beta-cyclodextrin, 2.5% v/v dimethylsulphoxide solution). Renal function was monitored using standard renal clearance methods. 3. Icatibant (10 microg/kg) had no significant effects on systemic haemodynamic variables (mean arterial pressure, heart rate or CO), renal haemodynamic variables (RBF or glomerular filtration rate), urine flow or sodium excretion. At 5 mg/kg plus 3 mg/kg per h, JA-2 also did not affect any of these variables, either after icatibant vehicle treatment or after icatibant treatment. 4. Our data do not support major roles for endogenous bradykinin or bradykinin degradation by EP 24.15/24.16 in the control of systemic and renal haemodynamics or renal excretory function in two-kidney, two-wrapped hypertension in rabbits.

Adrenergic beta-Antagonists↗

PubMed2001

Glomerular hypertension and hyperfiltration in adrenocorticotrophin-induced hypertension in rats: the role of nitric oxide.

OBJECTIVE: To determine the effects on pre- and post-glomerular vascular resistance of adrenocorticotrophin (ACTH)-induced hypertension in rats, before and after blockade of nitric oxide formation. DESIGN: Four groups of Sprague-Dawley rats were studied. Measurements were made in ACTH- (Synacthen Depot, 0.25 mg/kg twice daily for 8 days) and sham-treated anaesthetized rats, before and after either Nomega-nitro-L-arginine (L-NNA, 6 mg/kg) or vehicle. METHODS: Whole-kidney and single-nephron haemodynamics and function were measured. Glomerular capillary pressure was estimated from tubular stop-flow pressure measurements. RESULTS: Blood pressure (P < 0.001), renal blood flow (RBF, P < 0.05) and glomerular filtration rate (P < 0.01) were increased following ACTH treatment compared with sham. There were no differences in either total renal, or pre- or post-glomerular vascular resistances, but stop-flow-estimated glomerular capillary pressure was elevated (P < 0.001) as was single-nephron glomerular filtration rate (SNGFR) (P < 0.001) and single-nephron blood flow (P < 0.01 ) in the ACTH- compared to the sham-treated rats. L-NNA treatment increased blood pressure by a similar extent in both ACTH- and sham-treated rats, but reduced RBF (P < 0.05) and glomerular filtration rate (GFR) (P < 0.05) more in the ACTH group; similar changes were seen in single-nephron values. L-NNA increased pre- and post-glomerular resistances to a greater extent in the ACTH group. CONCLUSIONS: ACTH-induced hypertension produced glomerular hypertension and hyperfiltration, which may be due to nitric oxide-related vasodilatation of the renal vasculature.

Adrenocorticotropic Hormone↗

PubMed2001

Effects of activation of vasopressin-V1-receptors on regional kidney blood flow and glomerular arteriole diameters.

OBJECTIVES: We tested whether vasoconstriction of juxtamedullary glomerular arterioles contributes to vasopressin V1 -receptor-mediated reductions in medullary perfusion (MBF). DESIGN AND METHODS: The left kidney of pentobarbitone anaesthetized rabbits was denervated, a perivascular flow probe placed around the renal artery and laser-Doppler flow probes positioned in the inner medulla and on the cortical surface. Rabbits then received a 30 min intravenous infusion of [Phe2,Ile3,Orn8]vasopressin (V1 -AG; 30 ng/kg per min; n = 7) or its vehicle (n = 7). Kidneys were perfusion fixed at the final recorded mean arterial pressure (MAP) and filled with methacrylate casting material. Diameters of afferent and efferent arterioles were determined by scanning electron microscopy. RESULTS: V1 -AG increased MAP (19 +/- 3%) and reduced MBF (30 +/- 8%) but not cortical perfusion or total renal blood flow. Vehicle-treatment did not significantly affect these variables. After vehicle- and V1-AG-treatment, juxtamedullary afferent arteriole luminal diameter averaged 15.35 +/- 1.31 and 15.88 +/- 1.86 microm, respectively (P= 0.92), while juxtamedullary efferent arteriole luminal diameter averaged 17.75 +/- 1.86 and 18.36 +/- 2.24 microm, respectively (P= 0.93). CONCLUSIONS: V1-AG reduced MBF but did not significantly affect juxtamedullary arteriolar diameter. Our results therefore do not support a role for juxtamedullary arterioles in producing V1-receptor-mediated reductions in MBF, suggesting that downstream vascular elements (e.g. outer medullary descending vasa recta) might be involved.

Animals↗

PubMed2001

Chronic angiotensin converting enzyme inhibition enhances renal vascular responsiveness to acetylcholine in anaesthetized rabbits.

OBJECTIVE: To determine whether 6 weeks continuous treatment with an angiotensin converting enzyme (ACE) inhibitor reduced renal vascular responsiveness in vivo, since this treatment results in extensive phenotypic conversion of afferent arteriolar cells from contractile to endocrine-like, renin secretory cells. METHODS: Enalapril (10 microg/kg per h s.c.) was delivered continuously for 6 weeks. In anaesthetized rabbits (treated or sham), arterial blood pressure and renal blood flow were measured and renal responsiveness tested by constructing dose-response curves to bolus doses of phenylephrine, angiotensin II and acetylcholine delivered directly into the renal artery. RESULTS: ACE inhibition resulted in a significant shift to the left in the renal vascular conductance responses to acetylcholine (P < 0.005) and angiotensin II (P < 0.05), indicating enhanced, not reduced, responsiveness to these agents. There were no significant effects of chronic ACE inhibition on the conductance responses to phenylephrine. CONCLUSIONS: Contrary to our hypothesis, 6 weeks ACE inhibition did not reduce renal vascular responsiveness to three vasoactive agents, suggesting that the phenotypic changes observed in the afferent arterioles and to a lesser extent the interlobular arteries, were either insignificant or compensated for by other changes in renal circulatory control.

Acetylcholine↗

PubMed2001

Differential control of intrarenal blood flow during reflex increases in sympathetic nerve activity.

The role of renal sympathetic nerve activity (RSNA) in the physiological regulation of medullary blood flow (MBF) remains ill defined, yet regulation of MBF may be crucial to long-term arterial pressure regulation. To investigate the effects of reflex increases in RSNA on intrarenal blood flow distribution, we exposed pentobarbital sodium-anesthetized, artificially ventilated rabbits (n = 7) to progressive hypoxia while recording RSNA, cortical blood flow (CBF), and MBF using laser-Doppler flowmetry. Another group of animals with denervated kidneys (n = 6) underwent the same protocol. Progressive hypoxia (from room air to 16, 14, 12, and 10% inspired O(2)) significantly reduced arterial oxygen partial pressure (from 99 +/- 3 to 65 +/- 2, 51 +/- 2, 41 +/- 1, and 39 +/- 2 mmHg, respectively) and significantly increased RSNA (by 8 +/- 3, 44 +/- 25, 62 +/- 21, and 76 +/- 37%, respectively, compared with room air) without affecting mean arterial pressure. There were significant reductions in CBF (by 2 +/- 1, 5 +/- 2, 11 +/- 3, and 14 +/- 2%, respectively) in intact but not denervated rabbits. MBF was unaffected by hypoxia in either group. Thus moderate reflex increases in RSNA cause renal cortical vasoconstriction, but not at vascular sites regulating MBF.

Anesthesia↗

PubMed2000

Diversity of responses of renal cortical and medullary blood flow to vasoconstrictors in conscious rabbits.

The medullary microcirculation receives only about 10% of total renal blood flow, but plays a critical role in long-term arterial pressure regulation, so we need to better understand its regulation. Although there is evidence that circulating and locally acting hormones can differentially affect cortical and medullary blood flow in anaesthetized animals, there is little information from studies in conscious animals. This study is aimed (i) to develop a method for chronic measurement of cortical and medullary blood flow in conscious rabbits, and (ii) to test whether renal cortical and medullary blood flow can be differentially affected by intravenous (i.v.) infusions of various vasoconstrictor hormones in conscious rabbits. At preliminary operations, rabbits were equipped with single-fibre laser-Doppler flowprobes in the (left) renal cortex and medulla, and Transonic flowprobes for measuring cardiac output and renal blood flow. Intravenous angiotensin II (300 ng kg(-1) min(-1)), [Phe2,Ile3,Orn8]-vasopressin (30 ng kg(-1) min(-1)), noradrenaline (300 ng kg(-1) min(-1)), endothelin-1 (20 ng kg(-1) min(-1)) and N G-nitro-L-arginine (10 mg kg(-1)) increased mean arterial pressure (by 10-45% of baseline) and reduced heart rate (by 16-35%) and cardiac output (by 16-45%). Consistent with previous observations in anaesthetized rabbits, all treatments except [Phe2,Ile3, Orn8]-vasopressin reduced renal blood flow (13-63%) and cortical blood flow (16-47%), but medullary blood flow was significantly reduced only by [Phe2,Ile3,Orn8]-vasopressin (41%) and N G-nitro-L-arginine (42%). The diversity of these responses of cortical and medullary blood flow to i.v. infusions of vasoconstrictors provides further evidence for physiological roles of circulating and local hormones in the differential regulation of regional kidney blood flow.

Animals↗

PubMed2000

Sex differences in pressure diuresis/natriuresis in rabbits.

We tested for sex-related differences in the pressure diuresis/natriuresis relationships in anaesthetized, renally denervated rabbits, using an extracorporeal circuit to perfuse the left kidney with the rabbit's own blood, through a series of step-wise increases in renal artery pressure (RAP) (from 65 to 130 mmHg). Urine flow, sodium excretion, and the fractional excretions of sodium and urine increased with increasing RAP, and were greater in male than in female rabbits at all levels of RAP-tested. However, these apparent sex-related differences in the acute pressure diuresis/natriuresis relationships were not reflected in alterations in chronic regulation of mean arterial pressure (MAP). Thus, in rabbits on a normal salt diet (0.85 g day(-1)), resting conscious MAP was significantly greater in males (87 +/- 3 mmHg) compared with females (77+/-1 mmHg). Chronically increasing daily salt intake to 4.98 g day(-1) for 28 days had no significant effect on resting conscious MAP in either sex. Thus, although our observations indicate sex differences, at least under the present experimental conditions, in the factors regulating extracellular fluid volume, these do not appear to have a major impact in setting the level of MAP in the long term.

Anesthesia↗

PubMed2000

Effects of angiotensin II on regional afferent and efferent arteriole dimensions and the glomerular pole.

The diversity of renal arteriole diameters in different cortical regions has important consequences for control of glomerular capillary pressure. We examined whether intrarenal angiotensin II (ANG II; 0.1, 1, or 5 ng. kg(-1). min(-1)) in anesthetized rabbits acts preferentially on pre- or postglomerular vessels using vascular casting. ANG II produced dose-related reductions in afferent and efferent diameters in the outer, mid, and inner cortex, without effecting arterial pressure. Afferent diameter decreased more than efferent in the outer and mid cortex (P < 0.05) but by a similar extent in juxtamedullary nephrons (P = 0.58). Calculated efferent resistance increased more than afferent, especially in the outer cortex (127 vs. 24 units; 5 ng. kg(-1). min(-1) ANG II). ANG II produced significant dose-related increases in the distance between the arterioles at the entrance to the glomerular pole in all regions. Thus afferent diameter decreased more in response to ANG II, but efferent resistance rose more due to smaller resting luminal dimensions. The results also indicate that glomerular pole dimensions change in response to ANG II.

Angiotensin II↗

PubMed2000

Renovascular hypertension: structural changes in the renal vasculature.

Experimental narrowing of the main renal artery to produce hypertension increases the aorta-glomerular capillary pressure difference and vascular resistance. This article examines the hypothesis that hypertension also may be caused by structural changes that narrow intrarenal blood vessels, similarly increasing preglomerular vascular resistance and the aortic-glomerular capillary pressure gradient. There is evidence of both wall hypertrophy and lumen narrowing of the preglomerular arteries in spontaneously hypertensive rats, with increased preglomerular resistance and aortic-glomerular capillary pressure difference. We have also attempted to induce structural changes in renal-preglomerular vessels experimentally by infusing angiotensin II at low doses (0.5 to 4.5 ng/kg per minute) into the renal artery of Sprague-Dawley rats and greyhound dogs for up to 4 weeks. This angiotensin II infusion produced apparent dose-related effects on preglomerular vessel structure and hypertension. The possibility that hypertension may be induced by structural changes in preglomerular resistance vessel walls, by simulation of the hemodynamic effects of main renal artery stenosis, deserves further investigation.

Angiotensin II↗

PubMed1994

Intrarenal haemodynamic and glomerular responses to inhibition of nitric oxide formation in rabbits.

1. The renal effects of inhibiting nitric oxide (NO) formation using N-nitro-L-arginine (NOLA, 20 mg kg-1) were examined using micropuncture techniques in pentobarbitone-anaesthetized rabbits. 2. Renal vascular resistance doubled from 2.7 +/- 0.5 to 5.0 +/- 1.1 mmHg ml-1 min-1 after NOLA (P < 0.01), with similar percentage increases in both pre- (149 +/- 38%, P < 0.01) and postglomerular (158 +/- 42%, P < 0.01) resistance. 3. Glomerular capillary pressure rose from 33 +/- 1 to 40 +/- 1 mmHg after NOLA (P < 0.01) but despite this, glomerular filtration rate (GFR) and single nephron glomerular filtration rate did not significantly change. 4. Blood pressure increased 18 +/- 1 mmHg (P < 0.001) within 10 min of NOLA administration and remained near this level for the next 90 min. 5. The glomerular ultrafiltration coefficient (Kf) decreased significantly from 0.085 +/- 0.022 to 0.035 +/- 0.006 nl s-1 mmHg-1 (P < 0.05). 6. Urine flow and sodium excretion increased markedly (26 +/- 9 to 337 +/- 102 microliters min-1 and 5 +/- 2 to 342 +/- 12 mumol min-1 respectively, (P < 0.001)) and sodium fractional excretion rose from 1.0 +/- 0.3 to 8.0 +/- 2.2% (P < 0.01). 7. Thus, administration of NOLA to rabbits caused vasoconstriction of both pre- and postglomerular vessels, diuresis and natriuresis without significant change in GFR, and a reduction in Kf. The results suggest that NO may play an important role in the regulation of renal haemodynamics and glomerular function.

Animals↗

PubMed1994

Renal denervation potentiates the natriuretic and diuretic effects of atrial natriuretic peptide in anaesthetized rabbits.

1. The role of the renal nerves in modulating the action of atrial natriuretic peptide (ANP) in the kidney was studied by comparing the responses to ANP in innervated and surgically denervated kidneys in anaesthetized rabbits. 2. A low dose of ANP (0.05 microgram/kg per min, i.v.) was used to minimize the confounding effects of systemic hypotension. 3. The natriuretic and diuretic responses to ANP were significantly greater in denervated kidneys than in kidneys with intact innervation. Sodium excretion from denervated kidneys rose by 7.49 +/- 3.11 mumol/min in response to ANP (approximately 55%, P < 0.05) compared to 0.84 +/- 0.59 mumol/min (approximately 28%, NS) in innervated kidneys. Urine flow increased markedly in denervated kidneys by 73.2 +/- 29.9 mumol/min (approximately 60%, P < 0.05) but not in innervated kidneys. 4. Fractional sodium excretion increased significantly in denervated kidneys in response to ANP (median 2.3% to median 3.0%, P < 0.05). 5. Renal blood flow, glomerular filtration rate (GFR) and glomerular capillary pressure were unchanged in response to ANP in either denervated or innervated kidneys. Pre-glomerular vascular resistance fell in denervated kidneys during ANP infusion. 6. The natriuresis and diuresis observed in the denervated kidneys, due to an increased fractional excretion of sodium without increases in GFR or glomerular capillary pressure, is consistent with effects of ANP on tubular reabsorption of sodium. 7. Thus, ANP produced a natriuresis and diuresis at a low dose in denervated but not in innervated kidneys. This indicates that reflex activation of renal nerves may antagonize the renal effects of ANP.

Animals↗

PubMed1992

Morphometric analysis of the actions of angiotensin II on renal arterioles and glomeruli.

To study the effects of angiotensin II on afferent and efferent arteriole diameters and on intraglomerular dimensions, angiotensin II (20 ng.kg-1.min-1) or saline vehicle was infused intravenously for 20 min into anesthetized rabbits pretreated with enalapril. Both kidneys were perfusion fixed (glutaraldehyde), and vascular casts were made of the right kidneys using methacrylate. Morphometric analysis of the left kidneys using transmission electron microscopy revealed no significant effects of angiotensin II within the glomerulus, including the degree of mesangial contraction. The diameters of the afferent and efferent arteriole casts from the right kidneys were measured at 20, 50, and 75 microns from the glomerulus by scanning electron microscopy. In the outer cortex the mean diameters of the afferent and efferent arterioles were 14.1 +/- 0.8 and 9.7 +/- 0.5 microns, respectively, in the angiotensin II-infused rabbits, significantly less than in the control (vehicle) rabbits, 17.0 +/- 0.7 microns (P less than 0.001) and 10.7 +/- 0.4 microns (P less than 0.005), respectively. Calculation of the relative changes in vascular resistance, however, indicated that the effects of angiotensin II on efferent arteriole resistance (average difference 2.4 +/- 1.2 units/microns) were significantly greater per unit length than the effects on afferent arteriole resistance (average difference 0.9 +/- 0.3 units/microns). Thus infused angiotensin II caused greater reduction in afferent arteriolar diameter than in efferent, but the calculated increase in vascular resistance per micron was greater in efferent vessels due to their smaller resting diameter.

Angiotensin II↗

PubMed1991

Glomerular ultrafiltration in rabbits with superficial glomeruli.

The determinants of glomerular ultrafiltration in superficial glomeruli of a strain of English cross-breed rabbits have been studied using micropuncture techniques. Mean arterial blood pressure in the anaesthetised rabbits was 70 +/- 2 mmHg. The glomerular filtration rate in the kidney prepared for micropuncture was 4.4 +/- 0.4 ml/min, the filtration fraction was 22 +/- 1% and renal blood flow was 33 +/- 3 ml/min, and these values were comparable to values in conscious rabbits. Glomerular capillary pressure (Pgc) averaged 31 +/- 1 mmHg, the single-nephron glomerular filtration rate (SNGFR) averaged 25 +/- 2 nl/min, and the mean ultrafiltration pressure (calculated using the whole-kidney filtration fraction) averaged 7 +/- 1 mmHg. A net positive pressure at the efferent end of the glomerular capillaries (4.4 +/- 0.9 mmHg) indicated that a state of filtration pressure disequilibrium existed, under the experimental conditions of this study, in rabbit glomeruli. The calculated glomerular ultrafiltration coefficient (Kf) was 0.08 +/- 0.01 nl s-1 mmHg-1. Thus, compared to the Munich-Wistar rat, SNGFR is lower in the rabbit. This reflects the substantially lower glomerular ultrafiltration pressure in the rabbit, although this was offset partially by a higher Kf.

Animals↗

PubMed1991

Evidence for a renomedullary vasodepressor system in rabbits and dogs.

Renal perfusion was increased in anesthetized rabbits and dogs by using an extracorporeal circuit. When left kidney perfusion pressure was raised in rabbits (145-240 mm Hg), arterial pressure fell by 1.34 +/- 0.20 mm Hg/min. Pretreatment of the rabbits with 2-bromoethylamine hydrobromide, which destroyed the renal medulla, abolished the fall in arterial pressure (-0.08 +/- 0.08 mm Hg/min) in response to increased renal perfusion pressure. In dogs (with blockade of autonomic ganglia by pentolinium, converting enzyme inhibition [captopril/enalaprilat], and surgical renal denervation), increasing renal perfusion pressure to 170-220 mm Hg resulted in a fall in arterial pressure by 0.32 +/- 0.03 mm Hg/min (or by 28.9 +/- 3.1 mm Hg over a 90-minute period). Mean arterial pressure did not change significantly in identically prepared dogs not subjected to increased renal perfusion pressure, whereas pretreatment of dogs with bromoethylamine abolished the hypotensive response to increased renal perfusion pressure. Thus, the hypotensive response to increased renal perfusion was dependent on the presence of an intact renal medulla, but hypotension still occurred in the presence of converting enzyme inhibition, autonomic ganglion blockade, and renal denervation. The results provide in vivo evidence in two species that a vasodepressor factor from the renal medulla is released in response to increased renal perfusion.

Animals↗

PubMed1990

Vascular actions of endothelin in the rabbit kidney.

1. The effect of two doses of endothelin, 10 and 50 ng/kg per min, i.v., on glomerular filtration rate (GFR), tubular stop flow pressure and pre- and post-glomerular vascular resistance have been studied in anaesthetized rabbits. 2. Blood pressure did not change significantly in response to 10 ng/kg per min endothelin or vehicle infusion, but rose steadily during infusion of 50 ng/kg per min endothelin, increasing 11.8 +/- 2.7 mmHg by 90 min of infusion. 3. Glomerular filtration fraction (3H-inulin extraction ratio) rose and remained elevated throughout the endothelin infusion at 50 ng/kg per min. GFR did not change significantly until 70-90 min of the infusion (50 ng/kg per min) when it decreased by about 35%. No significant changes were seen at 10 ng/kg per min endothelin. 4. Sodium excretion rate rose in response to the lower dose, due to an increase in fractional sodium excretion. No changes in sodium excretion were seen at the higher dose of endothelin. 5. Glomerular capillary pressure rose significantly in response to endothelin infusion (50 ng/kg per min). 6. Renal blood flow fell progressively in response to endothelin (50 ng/kg per min), to about one-third of the pre-infusion value. 7. Renal vascular resistance increased progressively with both doses of endothelin, by about 35% at 10 ng/kg per min and about 400% at 50 ng/kg per min after 70-90 min. Preglomerular resistance increased from 1.0 +/- 0.1 to 5.0 +/- 1.9 mmHg/mL per min in response to endothelin 50 ng/kg per min. Postglomerular resistance rose from 1.0 +/- 0.1 to 5.6 +/- 2.17 mmHg/mL per min. 8. Thus endothelin infusion caused progressive renal vasoconstriction with similar magnitude increases in both pre- and postglomerular vessels. The vasoconstriction of the kidney caused by endothelin occurred at a dose which did not effect systemic blood pressure.

Animals↗