Resetting of renal autoregulation in conscious dogs: angiotensin II and alpha1-adrenoceptors

It has recently been shown, that common carotid occlusion (CCO) impairs autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR). This study was designed to investigate the mechanisms by which a moderate sympathetic stimulus influences RBF and GFR autoregulation. CCO provided a moderate sympathetic stimulus, and impaired autoregulation by increasing the lower autoregulatory limit of RBF and GFR by 21–30 mmHg. Basal RBF and GFR were not affected. A low-dose intrarenal infusion of the ₁-adrenoceptor agonist methoxamine (which did not change total RBF or GFR) induced a similar shift as CCO (n=5, RBF: +31±11 mmHg, P<0.05; GFR: +24±4 mmHg, P<0.01). In another group it was shown, that a combination of CCO with an intrarenal angiotensin II (A II) blockade (saralasin) did not significantly alter the response to CCO (n=7). These data suggest an ₁-adrenergic pathway for the sympathetic resetting of autoregulation. An augmented A II formation does not play a major role in mediating this effect.     

The effect of indomethacin on autoregulation of renal blood flow in the anasthetized dog.

1. Renal blood flow autoregulation was studied in anaesthetized greyhounds, using an electromagnetic flowmeter, before and after the administration of the prostaglandin-synthesis inhibitor, indomethacin, or phosphate buffer. 2. Indomethacin caused a reduction in renal blood flow at all levels of perfusion pressure, but did not affect the ability of the kidney to autoregulate. 3. The aburpt reinstatement of renal perfusion pressure from previously reduced levels caused a triphasic transient response in flow. Peak hyperaemia at the beginning of the transient was not affected by indomethacin. After indomethacin, the second phase of this flow transient showed an oscillatory pattern during which flow fell initially to levels significantly lower than control. 4. It is concluded that although indomethacin did not abolish steady-state autoregulation, renal prostaglandins may damp rapid oscillations in renal blood flow and thus contribute to the efficiency of autoregulation.     

Role of L-arginine uptake mechanisms in renal blood flow responses to angiotensin II in rats

Aim: Reduced muscle force greater than expected from loss of muscle mass has been reported in ageing muscles. Impaired sarcoplasmic reticulum (SR) Ca²⁺ release has been implicated as a possible mechanism, and attributed to several factors, including loss of ryanodine receptor (RYR) expression and protein binding. The aim of this study was to evaluate muscle quality and SR Ca²⁺ release in ageing rats that were not so old that major atrophy had occurred. Methods: We collected in situ force data from the plantarflexor muscle group and muscle mass from the constituent muscles to determine muscle quality (force/mass) in adult (6–8 months) and ageing (24 months) rats (n = 8/group). We evaluated SR Ca²⁺ uptake and release, and determined expression of key proteins associated with Ca²⁺ release [RYR and FK506 binding protein (FKBP)] and uptake (SERCA, parvalbumin, calsequestrin). Results: Plantarflexor force and muscle quality were reduced with ageing (approx. 28 and 34%, respectively), but atrophy was limited, and significant only in the medial gastrocnemius (approx. 15%). The fast phase of SR Ca²⁺ release was reduced with ageing in both gastrocnemii, as was FKBP expression and FKBP–RYR binding, but RYR expression was not affected. Similar, but non‐significant changes were present in the plantaris, but the soleus muscle generally showed no ageing‐related changes. Conclusion: These data suggest a possible role for impaired SR Ca²⁺ release in ageing‐related loss of muscle quality, although not through loss of RYR expression.     

Autoregulation of cerebral blood flow during early experimental renal hypertension in the conscious dog

Using the radioactive microsphere technique, cerebral blood flow (CBF) was measured in six conscious dogs before intervention and again on the 3rd-5th days after inducing hypertension by the one-kidney Goldblatt (1-KGH) procedure. Sham-operated controls were also studied. The normal temporal variability of CBF, as well as the precision of the microsphere technique in measuring CBF were also determined in other normal dogs. A left atrial catheter was used for the microsphere injections (15 micrometer diam spheres) and an aortic catheter was used for cardiac output and blood pressure measurements. On the 3rd-5th days after 1-KGH, mean aortic pressure increased from a control value of 94 +/- 7 mmHg to 135 +/- 20 mmHg (P less than 0.005). CBF did not change significantly from the control flow of 57.1 +/- 7.9 ml/100 g per min. Calculated cerebral vascular resistance increased by 47 percent (P less than 0.025) above the control value. Hence, the early phase of experimental renal hypertension is associated with adequate autoregulation of cerebral blood flow.     

Intrarenal angiotensin I conversion at normal and reduced renal blood flow in the dog

Intrarenal conversion of angiotensin I (ANG I) to angiotensin II (ANG II) under conditions of normal and reduced renal blood flow (RBF) elicited by constriction of the renal artery was examined in pentobarbital-anesthetized dogs. In eight animals, tracer doses of 125I-ANG I (5-12 pmol) were injected into the renal artery and 125I-ANG I, 125I-ANG II, and 125I-labeled metabolites were measured in renal venous effluent by high-voltage paper electrophoresis. The mean conversion of ANG I to ANG II during a single passage through the kidney was 21.8 +/- 2.1% at control RBF. When RBF was decreased by 25 and 53%, percent ANG I conversion was not altered significantly. In six dogs percent conversion of 125I-[Sar1, Ile5]ANG I, an ANG I analogue refractory to hydrolysis by aminopeptidases, was 18.1 +/- 1.7% at control RBF and did not change significantly when the RBF was reduced by 55%. Although there were severalfold increases in renal renin secretion rate and net ANG I generation rate during reduced RBF, net renal ANG II formation rate did not change significantly. These data indicate that there is substantial conversion of ANG I in a single passage through the dog kidney and that intrarenal ANG I conversion is independent of RBF even under conditions in which renin secretion rate and ANG I generation rate are increased severalfold.     

Influence of the renin-angiotensin system on the autoregulation of renal blood flow and glomerular filtration rate in conscious dogs

Renal autoregulation of blood flow (RBF) and glomerular filtration rate (GFR) were examined in 10 conscious foxhounds under a normal sodium diet before and after a continuous intrarenal converting-enzyme inhibition (CEI) or during the application of the angiotensin II antagonist saralasin. In order to prevent alpha-adrenergic interference, phenoxybenzamine was infused into the renal artery. In contrast to studies performed in salt depleted dogs there was no impairment of RBF or GFR autoregulation after CEI or saralasin. Renal blood flow was autoregulated at a level of 3.81 +/- 0.18 ml min-1 g-1 in the control group, 3.98 +/- 0.16 ml min-1 g-1 after CEI and 3.97 +/- 0.41 ml min-1 g-1 after saralasin. The lowest point of autoregulation was very much the same between the individual groups (control: 65.0 +/- 1.4 mmHg; CEI: 66.5 +/- 4.6 mmHg; saralasin: 67.4 +/- 3.2 mm Hg). GFR acted in a similar manner (autoregulation level control: 0.50 +/- 0.03 ml min-1 g-1; CEI: 0.52 +/- 0.05 ml min-1 g-1; saralasin. 0.50 +/- 0.04 ml min-1 g-1). The lowest pressure of GFR autoregulation differed slightly more (control: 81.5 +/- 2.2 mmHg; CEI: 93.2 +/- 4.2 mmHg; saralasin: 85.9 +/- 2.1 mmHg). The results suggest that the renal autoregulation of GFR and RBF is independent of the renin-angiotensin system in conscious dogs during a normal sodium diet.     

Effect of an angiotensin II antagonist on autoregulation in the isolated dog kidney.

The effect of the specific angiotensin II antagonist (AIIA), [1-sarcosine-8-alanine]angiotensin II, on autoregulation of glomerular filtration rate (GFR) and renal blood flow (RBF) in an isolated dog kidney was examined. Infusing the AIIA into the renal artery at 1.9 mug/min inhibited the renal vasoconstrictor action of angiotension II infused simultaneously at 1.15 mug/min. Under conditions of constant renal arterial pressure the AIIA had no significant effect on sodium excretion, GFR, RBF, cortical blood flow distribution (microsphere method), or renin secretion in non-renin-depleted kidneys. Similarly, no agonist properties were observed when the AIIA was infused into renin-depleted kidneys. This dose of the AIIA did not impair the capacity of the isolated kidney to regulate GFR or RBF when renal arterial pressure was increased from 100 to 150 mmHg. Efficiency of autoregulation of GFR and RBF was 77 and 82% of that predicted for perfect autoregulation. These values are not significantly different from those of the isolated kidney not infused with the antagonist. It is concluded that the angiotensin II antagonist, [1-sarcosine-8-alanine]angiotensin II, has no significant agonist properties, that it antagonizes the renal vascular effects of exogenously administered angiotensin II, but does not impair renal autoregulation. These data provide no support for the hypothesis that the renin-angiotensin system mediates the autoregulation of GFR and RBF.     

Cardiovascular and renal effects of intracerebroventricular angiotensin II in conscious sheep

Effects on systemic and pulmonary haemodynamics, renal electrolyte excretion, and plasma concentration of vasopressin, catecholamines, electrolytes and proteins in response to intracerebroventricular infusions of [Val⁵]-angiotensin II (ANG II) at 1, 2 and 4 pmol kg^-1min^-1in isotonic saline for 30 min were studied in conscious sheep (n = 6). Vehicle control infusions were performed in four of the animals. All three doses of ANG II were expected to increase CFS concentration of the peptide above physiological levels. All ANG II infusions were noticed to be dipsogenic, but the animals were not allowed to drink freely until at the end of the experiments (at 120 min post-infusion). The systemic arterial blood pressure increased significantly only in response to 2 and 4 pmol kg^-1min^-1, concomitant with an increase of the systemic vascular resistance, whereas the cardiac output and heart rate remained unchanged. The central venous pressure increased only after administration of the highest ANG II dose, while pulmonary artery, and capillary wedge pressures were unaffected during all experiments. The plasma protein and K concentration fell in response to ANG II administration. Also here, the effects were significant only at 2 and 4 pmol kg^-1min^-1. The plasma levels of vasopressin, noradrenaline, adrenaline and dopamine did not change significantly in response to any of the infusions. The renal Na excretion increased by 100–400%, but not in a strictly dose-dependent manner. Much smaller and more variable effects were seen on the renal K excretion. We conclude that: (1) supraphysiological CSF ANG II levels are needed to cause a pressor effect when the peptide is administered via the intracerebroventricular route in conscious sheep; (2) the blood pressure is increased exclusively via peripheral vasoconstriction and; (3) increased vasopressin release does not contribute to the cardiovascular changes. The results also demonstrate that ANG II may cause haemodilution via a central site of action.     

脑血流自动调节功能的三单元模型

目的建立一个三单元集中参数模型来模拟脑血流的自动调节功能。方法根据Bloor的实验数据拟合了一条在脑血流自动调节功能中,反映脑血流量和平均动脉压之间关系的三次曲线,然后利用这一拟合曲线来确定模型中的不定常电阻元件。结果利用这一模型,对不同压力变化情况下的脑血流量变化进行了数值模拟。通过与实验数据进行了对比,发现这一不定常三单元模型能够较为简单地模拟脑血流自动调节功能。结论经过改造的这一三单元集中参数模型可以为脑血流自动调节功能及脑血管疾病的研究提供帮助。     

Cardiovascular and renal effects of intracerebroventricular angiotensin II in conscious sheep.

Effects on systemic and pulmonary haemodynamics, renal electrolyte excretion, and plasma concentration of vasopressin, catecholamines, electrolytes and proteins in response to intracerebroventricular infusions of [Val5]-angiotensin II (ANG II) at 1, 2 and 4 pmol kg-1 min-1 in isotonic saline for 30 min were studied in conscious sheep (n = 6). Vehicle control infusions were performed in four of the animals. All three doses of ANG II were expected to increase CFS concentration of the peptide above physiological levels. All ANG II infusions were noticed to be dipsogenic, but the animals were not allowed to drink freely until at the end of the experiments (at 120 min post-infusion). The systemic arterial blood pressure increased significantly only in response to 2 and 4 pmol kg-1 min-1, concomitant with an increase of the systemic vascular resistance, whereas the cardiac output and heart rate remained unchanged. The central venous pressure increased only after administration of the highest ANG II dose, while pulmonary artery, and capillary wedge pressures were unaffected during all experiments. The plasma protein and K concentration fell in response to ANG II administration. Also here, the effects were significant only at 2 and 4 pmol kg-1 min-1. The plasma levels of vasopressin, noradrenaline, adrenaline and dopamine did not change significantly in response to any of the infusions. The renal Na excretion increased by 100-400%, but not in a strictly dose-dependent manner. Much smaller and more variable effects were seen on the renal K excretion.(ABSTRACT TRUNCATED AT 250 WORDS)