Coronary haemodynamic effects of angiotensin II in mild essential hypertension in man.

1. The present investigation was carried out to elucidate the possible role of the renin-angiotensin system in modulating coronary vasomotor responses in eight patients with uncomplicated mild essential hypertension with no electrocardiographic-echocardiographic evidence of left ventricular hypertrophy. 2. Systemic and coronary haemodynamics were monitored at baseline and during intravenous infusion of angiotensin II at a subpressor dose (3 ng min-1 kg-1 for 15 min) and at a pressor dose (13 ng min-1 kg-1 for 15 min) both at rest and during handgrip exercise. Infusion of the subpressor dose of angiotensin II decreased coronary sinus blood flow at rest (207 +/- 10 versus 182 +/- 9 ml/min, P less than 0.05) without a significant change in mean arterial pressure, heart rate or mean right atrial pressure. The performance of handgrip at baseline and during infusion of the subpressor dose of angiotensin II resulted in 55% (321 +/- 13 versus 207 +/- 10 ml/min) and 44% (263 +/- 16 versus 182 +/- 9 ml/min) increases in coronary sinus blood flow, respectively, in response to comparable increments in the rate-pressure product. At rest, infusion of the pressor dose of angiotensin II increased both coronary sinus blood flow (235 +/- 11 versus 207 +/- 10 ml/min, P less than 0.01) and the rate-pressure product (134 +/- 5 versus 111 +/- 8 mmHg beats/min, P less than 0.01). The increase in coronary sinus blood flow during isometric exercise was less than control (309 +/- 18 versus 321 +/- 13 ml/min, P less than 0.01). 3. It is thus concluded that (1) the opposite effects of angiotensin II on coronary blood flow are dose-dependent, and that (2) angiotensin II competes with the ability of the coronary arteries to dilate during handgrip exercise.     

Dose-response study of the redistribution of intravascular volume by angiotensin II in man.

1. The response of systemic and regional haemodynamic indices to increasing infusion rates of angiotensin II (1, 3 or 10 ng min-1 kg-1) or placebo [5% (w/v) D-glucose] was studied in eight normal male subjects. 2. As compared with placebo, angiotensin II infusion caused an incremental rise in the serum angiotensin II level [14.5 +/- 7.7 (placebo) to 187.2 +/- 36.1 (10 ng of angiotensin II min-1 kg-1) pmol/l; mean +/- 95% confidence interval] associated with a stepwise increase in total peripheral resistance [880 +/- 42 (placebo) to 1284 +/- 58 (10 ng of angiotensin II min-1 kg-1) dyn s cm-5] and a progressive reduction in cardiac output [8.3 +/- 0.4 (placebo) to 7.0 +/- 0.4 (10 ng of angiotensin II min-1 kg-1) litres/min]. 3. A stepwise fall in renal blood flow was observed with increasing angiotensin II infusion rate [1302 +/- 65 (placebo) to 913 +/- 64 (10 ng of angiotensin II min-1 kg-1) ml/min]. In contrast, calf blood flow was unaffected by 1 ng or 3 ng of angiotensin II min-1 kg-1 and was significantly increased by 10 ng of angiotensin II min-1 kg-1 (P less than 0.01). 4. Calf venous capacitance was uninfluenced by 1 ng of angiotensin II min-1 kg-1, but was significantly increased by both 3 ng (P less than 0.005) and 10 ng (P less than 0.001) of angiotensin II min-1 kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of arginine vasopressin and angiotensin II in cardiovascular responses to combined acute hypoxemia and hypercapnic acidosis in conscious dogs.

The physiological relationship of increased circulating angiotensin II and vasopressin to circulatory changes during combined hypoxemia and hypercapnic acidosis is unclear. To evaluate the role(s) of angiotensin II and vasopressin, seven unanesthetized female mongrel dogs with controlled sodium intake (80 meq/24 h X 4 d) were studied during 40 min of combined acute hypoxemia and hypercapnic acidosis (PaO2, 36 +/- 1 mmHg; PaCO2, 55 +/- 2 mmHg; pH = 7.16 +/- 0.04) under the following conditions: (a) intact state with infusion of vehicles alone; (b) beta-adrenergic blockade with infusion of d,l-propranolol (1.0 mg/kg bolus, 0.5 mg/kg per h); of the vasopressin pressor antagonist d-(CH2)5Tyr(methyl)arginine-vasopressin (10 micrograms/kg); and (d) simultaneous vasopressin pressor and angiotensin II inhibition with the additional infusion of 1-sarcosine, 8-alanine angiotensin II (2.0 micrograms/kg per min). The rise in mean arterial pressure during the combined blood-gas derangement with vehicles appeared to be related to increased cardiac output, since total peripheral resistance fell. Beta-adrenergic blockade abolished the fall in total peripheral resistance and diminished the rise in cardiac output during combined hypoxemia and hypercapnic acidosis, but the systemic pressor response was unchanged. In addition, the rise in mean arterial pressure during the combined blood-gas derangement was unaltered with vasopressin pressor antagonism alone. In contrast, the simultaneous administration of the vasopressin pressor and angiotensin II inhibitors during combined hypoxemia and hypercapnic acidosis resulted in the abrogation of the overall systemic pressor response despite increased cardiac output, owing to a more pronounced fall in total peripheral resistance. Circulating catecholamines were increased during the combined blood-gas derangement with vasopressin pressor and angiotensin II blockade, suggesting that the abolition of the systemic pressor response in the last 30 min of combined hypoxemia and hypercapnic acidosis was not related to diminished activity of the sympathetic nervous system. These studies show that vasopressin and angiotensin II are major contributors to the systemic pressor response during combined acute hypoxemia and hypercapnic acidosis.     

The effect of insulin on the rise in blood pressure and plasma aldosterone after angiotensin II in normal man

1. The effect of an intravenous infusion of insulin [2.5 units h-1 (m2 of body surface area)-1] on the rise in blood pressure and plasma aldosterone after intravenous angiotensin II (5, 10, and 20 ng min-1 kg-1) was investigated in six healthy, sodium-loaded men. 2. Serum insulin reached 96.8 +/- 18.1 mu-units/ml (control: 7.0 +/- 1.5 mu-units/ml) and serum potassium fell from 4.2 +/- 0.2 mmol/l to 3.6 +/- 0.2 mmol/l (P less than 0.005). 3. Hyperinsulinaemia increased (P less than 0.05) the secretion of aldosterone during the largest dose of angiotensin II (20 ng min-1 kg-1), but had no effect on the rise in blood pressure after angiotensin II.     

Blood pressure dependency on vasopressin and angiotensin II in prazosin-treated conscious normotensive rats

The role of the sympathetic nervous system, angiotensin II and vasopressin in limiting the hypotensive effect of prazosin (0.25 mg i.v.) was investigated in conscious normotensive rats. Within 45 min, mean blood pressure fell from 120 +/- 1 to 98 +/- 1 mm Hg (mean +/- S.E.M., P less than .001) while pulse rate rose from 463 +/- 9 to 500 +/- 9 beats/min (P less than .01). The blood pressure response to prazosin tended to be most pronounced in the rats with the smallest increase in heart rate (r = 0.58, P less than .001). Plasma norepinephrine and epinephrine levels were higher in prazosin-treated rats than in the controls (P less than .001). In the animals receiving prazosin, plasma renin activity was 4 times (P less than .001) and plasma vasopressin 7 times (P less than .01) higher than in the controls. Blockade of angiotensin II with saralasin (10 micrograms/min) further decreased blood pressure of the prazosin-treated rats by 22 +/- 4 mm Hg (P less than .001). In contrast, dPVDAVP (25 micrograms), a vasopressin antagonist, had no effect. Prazosin decreased the pressor response to methoxamine (10 micrograms) by 80% (P less than .001) but not to angiotensin II (60 ng). However, prazosin enhanced the reflex bradycardia induced by angiotensin II (P less than .001). These data demonstrate that both the sympathetic and the renin angiotensin system are markedly stimulated by prazosin; they both appear to limit its acute hypotensive action. In contrast, although plasma vasopressin is also increased, its pressor action is effectively buffered, probably due to enhanced baroreflex sensitivity.     

Prostacyclin attenuates both the pressor and adrenocortical response to angiotensin II in human pregnancy

1. The effects of angiotensin II (ANG II) infusion without and with simultaneous infusion of prostacyclin (PGI2; 1.4 pmol min-1 kg-1; 5 ng min-1 kg-1) have been studied in 16 women in second-trimester pregnancy. Ten received one infusion of ANG II alone, followed by its infusion together with PGI2; the remainder received two identical infusions of ANG II alone as controls. 2. PGI2 administration was associated with a small fall in diastolic pressure (P less than 0.01) and a proportionally greater rise in heart rate (P less than 0.001). Small rises in basal plasma renin and ANG II concentrations and a fall in aldosterone concentration were not statistically significant. 3. The diastolic pressor response to ANG II was blunted during PGI2 infusion by comparison with controls (P less than 0.025); this diminution in response was greatest in patients who had initially been most sensitive to ANG II (P less than 0.02). 4. The evoked increment in plasma aldosterone during ANG II infusion was considerably reduced (P less than 0.005) in the presence of PGI2. 5. These data further support the hypothesis of a role for PGI2 in relation to the blunted pressor response to ANG II of normal pregnancy. The apparent inhibitory effects of PGI2 on aldosterone secretion may partly explain the previously described dissociation between the renin-angiotensin system and aldosterone in pregnancy.     

Effects of a specific antidiuretic agonist on cardiac output and its distribution in intact and anephric dogs

1. The specific antidiuretic agonist [4-valine, 8-D-arginine]vasopressin (VDAVP) was administered intravenously to seven conscious dogs at a rate of 10 ng min-1 kg-1. Cardiac output (aortic electromagnetic flowmeter), mean arterial pressure and regional blood flows (radioactive microspheres) were measured before and after 30 min of infusion. 2. Mean arterial pressure fell from 89.9 +/- 4.5 (mean +/- SEM) to 82.3 +/- 5.9 mmHg and cardiac output increased from 115.4 +/- 8.7 to 163.0 +/- 14.4 ml min-1 kg-1. Total peripheral resistance decreased from 41.6 +/- 3.7 to 27.8 +/- 3.6 units and heart rate increased from 79.2 +/- 5.9 to 123.2 +/- 5.9 beats/min. Blood flow increased significantly in the myocardium, fat and skeletal muscle vascular bed. 3. In another group of six dogs subjected to a similar protocol 24 h after bilateral nephrectomy, mean arterial pressure fell from 102.2 +/- 5.3 to 82.7 +/- 3.4 mmHg and cardiac output increased from 125.6 +/- 3.0 to 171.2 +/- 4.0 ml min-1 kg-1. Total peripheral resistance decreased from 39.3 +/- 3.4 to 23.4 +/- 1.3 units and heart rate increased from 84 +/- 4.9 to 113.3 +/- 4.3 beats/min. The increase in cardiac output and the fall in total peripheral resistance did not differ significantly between intact and anephric dogs. Regional blood flow responses differed in some respects in the two groups studied, but there was no evidence that the vasodilatory action of VDAVP depended on the presence of the kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)     

Biphasic blood pressure response to angiotensin II in the conscious rabbit: relation to prostaglandins

The injection of a large bolus of angiotensin II causes a biphasic blood pressure response in the conscious rabbit. To investigate contribution of prostaglandins (PGs) to the depressor phase of the blood pressure response, we studied the blood pressure effect of i.v. bolus injections of angiotensin II before and after the administration of an inhibitor of cyclooxygenase, indomethacin or sodium meclofenamate (10 mg kg-1), and in relation to associated changes in the plasma concentration of immunoreactive PGs. In conscious rabbits, angiotensin II (0.05-5.00 microgram kg-1) produced a dose-related pressor response which at both 1.5 and 5.0 micrograms kg-1 was followed by lowering of blood pressure to below the preinjection level. Neither indomethacin nor meclofenamate affected the maximal rise in pressure produced by angiotensin II, but both cyclooxygenase inhibitors augmented the duration of the pressor phase and abolished the depressor phase of the hemodynamic response to angiotensin II at 1.5 to 5.0 micrograms kg-1. After administration of angiotensin II, 5 micrograms kg-1, the plasma concentration of 6-keto-PGF1 alpha increased (P less than .01) from 218 +/- 21 pg/ml by 221 and 235% during the pressor and the depressor phases of the blood pressure response, respectively. Increments in plasma 6-keto-PGF1 alpha correlated inversely with the duration of the pressor phase and directly with the maximal lowering of blood pressure during the depressor phase. Plasma levels of PGE2 and PGF2 alpha also were increased by the peptide but the increments were not correlated with any aspect of the blood pressure response. These data suggest that a mechanism involving PGs both curtails the pressor phase and mediates the depressor phase of the hemodynamic response to pharmacological doses of angiotensin II in the conscious rabbit.     

The effect of captopril on blood pressure and angiotensins I, II and III in sodium-depleted dogs: problems associated with the measurement of angiotensin II after inhibition of converting enzyme

1. Changes in arterial blood pressure, blood angiotensin I, plasma angiotensin II and plasma angiotensin III were measured in conscious sodium-depleted dogs after infusion of captopril, an orally active inhibitor of converting enzyme. 2. Angiotensins II and III were measured after chromatography to remove angiotensin I, which increased in concentration after inhibition of converting enzyme and which interfered in the direct assay for angiotensin II. 3. Infusion of captopril at 20, 200, 2000 and 6000 microgram h-1 kg-1, each for 3 h, produced a rapid fall in blood pressure and in concentration of angiotensin II. Angiotensin II was undetectable at 6000 microgram h-1 kg-1 (mean pre-infusion value for all samples was 39 +/- SD 15 pmol/1, n = 14). 4. The percentage fall in blood pressure correlated with the percentage fall in plasma angiotensin II (r = 0.65, P < 0.001). 5. These results suggest that the initial fall in blood pressure may be mediated in part by the suppression of angiotensin II. 6. Blood angiotensin I concentration rose with each rate of infusion of drug to a maximum 16-fold increase at 6000 microgram h-1 kg-1 (26-416 pmol/l). The rise in angiotensin I was inversely related to the fall in angiotensin II (r = 0.68, P < 0.001).     

Angiotensin II increases the release of endothelin-1 from human cultured endothelial cells but does not regulate its circulating levels

We investigated the effect of angiotensin II on endothelin-1 secretion in vitro and in vivo. In vivo, angiotensin II was given intravenously to 23 essential hypertensive and 8 control subjects according to different protocols: Study A, 1.0 ng x min-1 x kg-1 and 3.0 ng x min-1 x kg-1 angiotensin II for 30 min each; Study B, 1.0 ng x min-1 x kg-1 and 3.0 ng x min-1 x kg-1 angiotensin II for 120 min each; Study C, 3.0 ng x min-1 x kg-1 angiotensin II for 30 min followed by a dose increment of 3.0 ng x min-1 x kg-1 every 30 min until mean blood pressure levels increased by 25 mmHg; Study D, 1.0 ng x min-1 x kg-1 followed by 3.0 ng x min-1 x kg-1 angiotensin II for 60 min each on two different NaCl diets (either 20 mmol NaCl/day or 220 mmol NaCl/day, both for 1 week). In all in vivo studies neither plasma nor urine endothelin-1 levels changed with angiotensin II infusion. In contrast, angiotensin II (10(-9), 10(-8), 10(-7) mol/l) stimulated endothelin-1 secretion from cultured human vascular endothelial cells derived from umbilical cord veins in a time- and dose-dependent manner. The in vitro angiotensin II effects were abolished by candesartan cilexetil, an inhibitor of the membrane-bound AT1 receptor, and also by actinomycin D, an RNA synthesis inhibitor, and cycloheximide, a protein synthesis inhibitor, indicating that endothelin-1 release depended on AT1 receptor subtype and de novo protein synthesis. Our findings indicate that angiotensin II regulates endothelin-1 release by cultured endothelial cells through an AT1 receptor-dependent pathway, but does not influence circulating endothelin-1 levels in vivo.     

Subcutaneous and muscle blood flow during dopamine infusion in man

Subcutaneous fat tissue and skeletal-muscle blood flow was measured in six male volunteers using the local 133Xe-washout method. Measurements were obtained before and during intravenous dopamine infusion in non-pressor (1 microgram kg-1 min-1) and pressor infusion rates (3-6 micrograms kg-1 min-1). During non-pressor infusion rate the systolic and diastolic arterial pressure and heart rate remained unchanged. When pressor dose dopamine was infused the systolic and mean arterial pressures increased significantly, whereas the diastolic pressure and the heart rate were left unchanged. The blood flow increased progressively from control values in both subcutis (control: 2.9 +/- 0.2, non-pressor: 5.0 +/- 1.6, pressor: 9.1 +/- 0.4 ml min-1 100 g-1, mean +/- SEM) and in skeletal muscle (control: 1.2 +/- 0.2, non-pressor: 1.5 +/- 0.2, pressor: 1.9 +/- 0.4 ml min-1 100 g-1, mean +/- SEM) and was significantly different from baseline values at any dopamine infusion rate. Side-effects were observed only at pressor dose infusion. It is concluded that dopamine in humans seems to possess vasodilatoric properties in subcutaneous fat tissue, and in skeletal muscles.     

Regional blood flows and cardiac function changes induced by angiotensin II in conscious dogs

Hemodynamic properties of angiotensin (ANG) II 1, 5, 10 and 100 ng/kg i.v. and 10, 100 and 1000 ng/kg i.v.t. were assessed in conscious dogs. ANG II i.v. produced a dose-dependent pressor response (59 +/- 5-124 +/- 16 mmHg) and renal vasoconstriction (1.3 +/- 0.4-96 +/- 32 mmHg/ml/min). Ganglionic blockade (chlorisondamine 2 mg/kg i.v.) diminished mean arterial responses without altering peptide effects on renal circulation. At the highest dose, ANG II i.v. induced cardiac stimulation: increased heart rate (75 +/- 4-115 +/- 6 beats/min), cardiac output (2.0 +/- 0.1-2.4 +/- 0.2 l/min), dP/dt (2308 +/- 181-2773 +/- 173 mmHg/sec) and coronary blood flow (49 +/- 10-96 +/- 23 ml/min). Although with chlorisondamine cardiac response was more pronounced, subsequent beta blockade abolished it. Concomitantly, an isolated increase in plasma epinephrine was recorded (63 +/- 8-1505 +/- 354 pg/ml). A pressor response (59 +/- 8-89 +/- 13 mmHg) and renal vasoconstriction (1.1 +/- 0.1-2.2 +/- 0.5 mmHg/ml/min) were also produced by ANG II i.v.t. at the highest dose. These centrally mediated changes were prevented by chlorisondamine. Our study demonstrates 1) i.v. ANG II-mediated pressor responses are dependent on direct and indirect components, the relative contribution of each being dependent on the regional circulation; ANG II i.v. also produced a biphasic cardiac response--an initial centrally mediated depression and a secondary stimulation dependent on epinephrine via cardiac beta receptors and 2) i.v.t. ANG II-mediated pressor effects are essentially indirect. Finally, no evidence was found to support the role of vasopressin in ANG II effects.     

Atrial natriuretic peptide inhibits the aldosterone response to angiotensin II in man

We have investigated the interaction between the recently discovered natriuretic factor alpha human atrial natriuretic peptide (alpha h-ANP) and the renin-angiotensin-aldosterone system in man. Angiotensin II infused with placebo produced a significant rise of plasma aldosterone concentration (mean +/- SEM increment 352 +/- 23 pmol/l, n = 7, P less than 0.001). The infusion of alpha h-ANP together with angiotensin II largely abolished the aldosterone response (P less than 0.001). Diastolic blood pressure rose in response to the infusion of angiotensin II with placebo (mean increment 21.0 +/- 0.9 mmHg, P less than 0.001). Systolic blood pressure increased to a lesser degree (mean increment 12.5 +/- 0.7 mmHg, P less than 0.001). The infusion of alpha h-ANP together with angiotensin II significantly blunted the diastolic pressor response (P less than 0.01). This ability of alpha h-ANP to blunt the pressor effect of angiotensin II may be important in the control of systemic blood pressure. The inhibition of angiotensin II-stimulated aldosterone release demonstrates that alpha h-ANP may not only be a circulating natriuretic factor in its own right but that it may also act as a modulator of a related endocrine system.     

Inhibition by bradykinin of the vascular action of angiotensin II in the dog kidney

In the dog anesthetized with pentobarbital, the effect of bradykinin on the lowering of renal blood flow produced by bolus injections of angiotensin II was studied. Injection into the renal artery of angiotensin II (0.06--0.50 microgram) caused vasoconstriction and decreased blood flow to the kidney in a dose-related manner. Renal arterial infusion of bradykinin (10 ng kg-1 min-1), prostaglandin (PG) E2 (4 ng kg-1 min-1) or PGI2 (4 ng kg-1 min-1) produced renal vasodilation and inhibited the vasoconstrictor effect of angiotensin II. However, renal arterial infusion of another vasodilatory peptide, substance P (2 ng kg-1 min-1), did not alter the effect of angiotensin II on the renal vasculature. Pretreatment of dogs with an inhibitor of PG synthesis, sodium meclofenamate (5 mg/kg), abolished the inhibitory effect of bradykinin on angiotensin II-induced renal vasoconstriction. In contrast, renal arterial infusion of either PGE2 or PGI2 was equally effective in reducing the renal vascular effect of angiotensin II in animals with and without meclofenamate pretreatment. These results suggest that bradykinin reduces the reactivity of the renal vasculature to angiotensin II by a mechanism dependent upon PG synthesis.     

(1-Sar, 8-Ile) angiotensin II in the treatment of inhalation injury: a pilot study.

The patients were three men and two women with moderate to severe inhalation injury. Each patient received immediate fluid therapy and all required intubation for respiratory management. At some time between 24 and 72 hours after the injury, the synthetic angiotensin analogue (1-Sar, 8-Ile) angiotensin II was infused at a rate of 100 ng/kg/min for 10 minutes, 200 ng/kg/min for another 10 minutes, and 300 ng/kg/min for 30 minutes. The mean (+/- SD) PaO2 increased from 80.8 +/- 26.9 mmHg before to 89.8 +/- 27.3 mmHg after the infusion (P < 0.05) and the PaCO2 decreased from 42.4 +/- 8.3 to 39.6 +/- 7.9 mmHg (P < 0.05). A transient pressor response was noted in all patients. The results suggest that this angiotensin II analogue may be of benefit in the treatment of inhalation injury and other types of acute lung injury.     

Role of AT1 receptors in the resetting of the baroreflex control of heart rate by angiotensin II in the rabbit.

Angiotensin II (Ang II) resets the baroreflex control of heart rate to a higher blood pressure. This action is apparently mediated via Ang II receptors in the area postrema, but it is not known if these are of the AT1 or AT2 subtype. In the present study the effects of losartan, a selective AT1 receptor antagonist, and PD 123319, a selective AT2 antagonist, on the cardiac baroreflex response to Ang II were investigated in conscious rabbits with chronically implanted arterial and venous catheters. Baroreflex curves were generated with intravenous infusions of phenylephrine and nitroprusside (2.6-25 micrograms/kg per min) and analyzed using a four-parameter logistic model to yield their upper and lower plateaus, arterial pressure at the midpoint of the heart rate range (BP50), and slope coefficient. From these four parameters, the gain and range of the baroreflex were calculated. Background intravenous infusion of Ang II at 10 ng/kg per min increased mean arterial pressure by 17 mmHg but did not change heart rate. Ang II shifted the baroreflex curve to the right as indicated by an increase in BP50 from 70.9 +/- 2.0 to 89.3 +/- 2.7 mmHg (P < 0.05), but did not change baroreflex gain significantly. Ang II did not alter the upper plateau of the baroreflex, but decreased the lower plateau from 119.4 +/- 10.3 to 73.6 +/- 11.5 beats per minute (bpm) (P < 0.05), extending the heart rate range by 52.5 bpm. Pretreatment with losartan completely abolished the pressor and cardiac baroreflex responses to Ang II. In contrast, PD 123319 had no effect on these responses. Administration of losartan alone to block endogenous Ang II shifted the baroreflex curve to the left as indicated by a decrease in BP50 from 71.2 +/- 2.7 to 64.7 +/- 2.5 mmHg (P < 0.05). These results demonstrate that the resetting of the baroreflex control of heart rate by Ang II is mediated by AT1 receptors, and that basal levels of endogenous Ang II exert a tonic action on the cardiac baroreflex to increase the setpoint around which the baroreflex regulates heart rate.     

Interaction between renal prostaglandins and angiotensin II in controlling glomerular filtration in the dog

Although previous studies suggest that the renal vasoconstrictor effects of angiotensin II (ANG II) are normally confined to the efferent arterioles, the mechanisms that prevent ANG II from constricting preglomerular vessels are still unclear. In the present study, the role of prostaglandins (PG) in protecting preglomerular vessels from ANG II constriction was examined in dogs with normal or non-filtering kidneys in which ANG II formation was blocked with captopril and renal artery pressure was servo-controlled at 75-80 mmHg. Before PG blockade (n = 6), ANG II infusion (20 ng min-1 kg-1) decreased renal blood flow (RBF) by 54 +/- 4%, but did not change glomerular filtration rate (GFR) significantly. After PG blockade (n = 6), ANG II infusion decreased GFR by 37 +/- 7% and RBF by 56 +/- 6%, while increasing calculated preglomerular resistance much more than before PG blockade. In another group of dogs, secondary changes in renal resistances, due to tubuloglomerular feedback, were prevented by occluding the ureter during mannitol diuresis until glomerular filtration ceased. After inhibition of tubuloglomerular feedback in non-filtering kidneys (n = 7), ANG II decreased RBF by 40 +/- 3% and increased glomerular hydrostatic pressure, estimated from stop-flow ureteral pressure and plasma colloid osmotic pressure, by 8.7 +/- 1.7 mmHg. Postglomerular resistance increased by 91 +/- 12% while preglomerular resistance was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of renal arterial pressure in the regulation of extracellular volume in conscious dogs.

1. This study in conscious dogs examined the quantitative effects of a reduction in the renal arterial pressure on the renal homeostatic responses to an acute extracellular fluid volume expansion. 2. Seven female beagle dogs were chronically instrumented with two aortic catheters, one central venous catheter and a suprarenal aortic cuff, and were kept under standardized conditions on a constant high dietary sodium intake (14.5 mmol of Na+ day-1 kg-1 body weight). 3. After a 60 min control period, 0.9% (w/v) NaCl was infused at a rate of 1 ml min-1 kg-1 body weight for 60 min (infusion period). Two different protocols were applied during the infusion period: renal arterial pressure was maintained at 102 +/- 1 mmHg by means of a servo-feedback control circuit (RAP-sc, 14 experiments) or was left free (RAP-f, 14 experiments). 4. During the infusion period, in the RAP-sc protocol as well as in the RAP-f protocol, the mean arterial pressure increased by 10 mmHg, the heart rate increased by 20 beats/min, the central venous pressure increased by 4 cmH2O and the glomerular filtration rate (control 5.1 +/- 0.3 ml min-1 kg-1 body weight, mean +/- SEM) increased by 1 ml min-1 kg-1. 5. Plasma renin activity [control 0.85 +/- 0.15 (RAP-f) and 1.08 +/- 0.23 (RAP-sc) pmol of angiotensin I h-1 ml-1] decreased similarly in both protocols.(ABSTRACT TRUNCATED AT 250 WORDS)     

Angiotensin II augments sympathetically mediated arteriolar constriction in man.

1. In animal studies, angiotensin II facilitates adrenergic neurotransmission by both pre- and post-synaptic mechanisms. We have investigated whether this interaction occurs in forearm resistance vessels in man. 2. The effect of arterial infusion of angiotensin II (320 fmol/min) on sympathetic vasoconstriction produced by lower-body negative pressure (15 mmHg) was studied in six subjects, and that on the response to exogenous noradrenaline (37.5-150 pmol/min) was studied in a further eight subjects. Forearm blood flow was measured by strain-gauge plethysmography. 3. The dose of angiotensin II was chosen to produce no alteration in resting blood flow, and those of noradrenaline were selected to provide a reduction in blood flow equivalent to that produced by lower-body negative pressure. 4. Lower-body negative pressure produced no change in heart rate or diastolic blood pressure, but caused an initial 5 mmHg fall in systolic blood pressure (P less than 0.01). Blood flow was reduced by 21 +/- 6% in both forearms by lower-body negative pressure during saline infusion. During angiotensin II infusion, there was a marked difference in the response to lower-body negative pressure, with blood flow being reduced by 40 +/- 7% in the infused arm, but only by 21 +/- 4% in the control arm (P less than 0.05). Angiotensin II infusion had no effect on resting blood flow or the responses to noradrenaline. 5. We conclude that angiotensin II augments sympathetic vasoconstriction in forearm resistance vessels in man at a concentration that has no direct effect on blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of intravenous infusion of adrenaline on the cardiovascular responses to distal body subatmospheric pressure in man

1. On two separate occasions, at least 1 week apart, seven young healthy male subjects received intravenous infusions of either adrenaline [0.27 nmol (50 ng) min-1 kg-1] or saline (154 mmol/l NaCl), plus ascorbic acid (5.68 mmol/l), over 30 min. 2. On each occasion, the subjects were exposed to distal body subatmospheric pressure (DBSP), 0 to 50 mmHg (0 to 6.65 kPa) in 10 mmHg (1.33 kPa) steps, before infusion, during the final 15 min of the infusion, and at 15 min and 30 min after the cessation of the infusion. 3. Venous adrenaline concentrations of 2.85 +/- 0.22 nmol/l were achieved during the adrenaline infusion, compared with 0.49 +/- 0.07 nmol/l during the saline infusion (P less than 0.001). At 15 min and at 30 min after cessation of the adrenaline infusion, venous adrenaline concentrations had fallen to levels similar to those achieved after the cessation of the saline infusion. 4. Heart rate rose significantly from 58 +/- 4 beats/min to 67 +/- 4 beats/min during the adrenaline infusion (P less than 0.05), but there was no further significant change in response to 50 mmHg (6.65 kPa) DBSP. At 30 min after the cessation of the adrenaline infusion, heart rate rose from 60 +/- 4 beats/min to 78 +/- 7 beats/min in response to 50 mmHg DBSP. This increase was significantly greater than that observed before the adrenaline infusion [58 +/- 4 beats/min to 69 +/- 7 beats/min during 50 mmHg (6.65 kPa) DBSP; P less than 0.01].(ABSTRACT TRUNCATED AT 250 WORDS)