This study compares the haemodynamic and hormonal responses during haemorrhage of conscious dogs pre-treated with an endothelin-A (ET-A) receptor inhibitor. The dogs were studied in two different randomized groups: the control group and a group that was given the ET-A receptor antagonist ABT-627 (as a bolus of 1mg·kg of body weight -1 followed by 0.01mg·kg body weight -1 ·min -1 intravenously). The time-course was the same for both groups: after a 1h baseline period (pre-haemorrhage), blood (25ml·kg of body weight -1 ) was withdrawn within 5min. Haemodynamics were continuously recorded and hormone levels measured after 1h (post-haemorrhage). Thereafter, the blood withdrawn was retransfused within 5min and haemodynamics again observed for 1h (post-retransfusion). In ABT-627-treated dogs, the decrease in mean arterial pressure from 87±3 to 64±3mmHg ( P <0.05 versus pre-haemorrhage), and cardiac output from 2.1±0.1 to 1.3±0.1l·min -1 ( P <0.05 versus pre-haemorrhage) and the increase in systemic vascular resistance from 3286±174 to 4211±230dyn·s·cm -5 ( P <0.05 versus pre-haemorrhage) during acute haemorrhage are comparable with controls. During haemorrhage in controls, vasopressin levels increased from 0±0 to 13±2pg·ml -1 ( P <0.05 versus pre-haemorrhage), angiotensin II levels increased from 9±1 to 28±9pg·ml -1 ( P <0.05 versus pre-haemorrhage) and adrenaline levels increased from 134±22 to 426±74pg·ml -1 ( P <0.05 versus pre-haemorrhage) whereas noradrenaline levels did not change (approx. 200 pg·ml -1 ). In ABT-627-treated dogs, vasopressin levels increased from 0.2±0.0 to 22.2±6.1pg·ml -1 ( P <0.05 versus pre-haemorrhage and P <0.05 versus control), angiotensin II levels increased from 8±1 to 37±8pg·ml -1 ( P <0.05 versus pre-haemorrhage), noradrenaline levels increased from 147±16 to 405±116pg·ml -1 ( P <0.05 versus pre-haemorrhage) and adrenaline levels did not change (200 pg·ml -1 ) during haemorrhage. We conclude from our results that dogs receiving the selective ET-A inhibitor ABT-627 seem to show a different hormonal response after haemorrhage compared with controls, displaying considerably higher noradrenaline concentrations. Independent of ET-A receptor inhibition, cardiac output during haemorrhage was maintained within the control range. This may indicate that the organism is defending blood flow (cardiac output) over blood pressure during haemorrhage, and that this defence strategy is not compromised by ET-A receptor inhibition.
1. We studied post-prandial changes in renal function in dogs adapted to either low or high sodium intake with and without concomitant post-prandial infusion of angiotensin II. Six trained dogs were exposed to diets containing either 0.5 or 14.5 mmol Na + day −1 kg −1 body weight (low or high sodium respectively). They were studied from 20 min before to 4 h after food intake. In half of the experiments a physiological dose of angiotensin II (4 ng min −1 kg −1 body weight) was administered after food intake for four post-prandial hours. The water intake was high and equal on both diets (91 ml day −1 kg −1 body weight) . 2. On a high-salt diet post-prandial sodium excretion and urine volume increased considerably above fasting values. This post-prandial increase was attenuated when angiotensin II was infused (post-prandial sodium excretion was 31% ± 3% of intake without versus 10% ± 1% with angiotensin II, post-prandial urine volume was 22% ± 2% without versus 8% ± 1% with angiotensin II, P < 0.05). Post-prandial increases in glomerular filtration rate and fractional sodium excretion were attenuated during angiotensin II infusion in dogs on a high-salt diet. 3. On a low-salt diet post-prandial sodium excretion remained low with or without angiotensin II infusion, whereas urine volume increased post-prandially, and this increase was greater when angiotensin II was administered (40% ± 3% versus 34% ± 2% of intake, P < 0.05) . 4. Angiotensin II infusion increased mean arterial pressure by an average of 12 mmHg in dogs on a high-salt diet ( P < 0.05) and by 7 mmHg in dogs on a low-salt diet. In dogs on a high-salt diet, right atrial pressure was on an average 3 cmH 2 O higher with than without angiotensin II ( P < 0.05). In animals on a low salt intake post-prandial right atrial pressure decreased slightly, but remained in the range of fasting values, during angiotensin II infusion. 5. Neither plasma osmolality nor plasma sodium concentration changed in any of the four protocols. 6. We conclude that the post-prandial effects of angiotensin II in dogs on a high water intake depend on the amount of concomitant sodium intake. Angiotensin II reduces the post-prandial diuresis and natriuresis when given to sodium-loaded dogs, whereas angiotensin II does not reduce post-prandial urine flow and sodium excretion rates in dogs on a low sodium intake and may even augment water excretion in this condition.
1. This study in conscious dogs examined the effects of extracellular volume expansion on plasma antidiuretic hormone, atrial natriuretic peptide and aldosterone concentrations, plasma renin activity, and haemodynamic and renal responses during controlled mechanical ventilation with 20 cmH 2 O positive end-expiratory pressure. 2. Twenty experiments (10 controls, 10 expansion experiments with 03 ml min −1 kg −1 body weight of a balanced electrolyte solution given intravenously throughout) were performed in five trained, conscious, tracheotomized dogs over 4 h: first and fourth hour, spontaneous breathing; second and third hour, 20 cmH 2 O positive end-expiratory pressure. 3. In the control experiments positive end-expiratory pressure increased plasma antidiuretic hormone concentration from 1.4 + 0.2 to 10.0 + 3.3 pg/ml, plasma aldosterone concentration from 113 + 19 to 258 + 58 pg/ml and heart rate from 77 + 5 to 94 + 5 beats/min. Positive end-expiratory pressure did not change plasma atrial natriuretic peptide concentration (55 + 5 pg/ml), plasma renin activity (2.6 + 0.4 pmol of angiotensin I h −1 ml −1 ) and mean arterial pressure 103 + 3 mmHg). 4. In the expansion experiments, positive end-expiratory pressure did not change plasma antidiuretic hormone concentration (1.1 + 0.1 pg/ml), plasma aldosterone concentration (25 + 2 pg/ml), plasma atrial natriuretic peptide concentration (82 + 8 pg/ml), plasma renin activity (0.8 + 0.15 pmol of angiotensin I h −1 ml −1 ), heart rate (92 + 6 beats/min) and mean arterial pressure (111 + 4 mmHg). 5. In the control experiments, urine volume, sodium excretion and fractional sodium excretion remained in a low range during positive end-expiratory pressure, whereas potassium excretion increased. In the expansion experiments, urine volume, sodium excretion and fractional sodium excretion increased continuously. Glomerular filtration rate was decreased during positive end-expiratory pressure in the control experiments when compared with the expansion experiments (3.4 + 0.3 versus 3.9 + 0.2 ml min −1 kg −1 body weight). 6. Arterial blood gases and plasma osmolality did not change in either protocol. 7. It is suggested that the striking increase in antidiuretic hormone may play a part in the circulatory control mechanisms that maintain mean arterial pressure during positive end-expiratory pressure when the extracellular volume is not expanded.
1. This study in conscious dogs examined the quantitative effects of a reduction in the renal arterial pressure on the renal homoeostatic 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 cmH 2 O 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. 6. Renal sodium excretion, fractional sodium excretion and urine volume increased more in the RAP-f experiments than in the RAP-sc experiments ( P <0.05), renal sodium excretion from 8.2 to 70.1 (RAP-f) and from 7.7 to 47.4 (RAP-sc) μmol min −1 kg −1 body weight, fractional sodium excretion from 1.1 to 8.0 (RAP-f) and from 1.0 to 5.4 (RAP-sc)% and urine volume from 39 to 586 (RAP-f) and from 38 to 471 (RAP-sc) μl min −1 kg −1 body weight. 7. In the RAP-f experiments as well as in the RAP-sc experiments, urinary sodium excretion increased with expansion of the extracellular fluid volume, which increased by a maximum of 21% (fasting extracellular fluid volume: 206 ± 4 ml/kg body weight, six dogs, 28 days). 8. The increase in renal arterial pressure contributed significantly to the renal homoeostatic response, as 21% less urine and 31% less sodium were excreted when the extracellular fluid volume was expanded and the renal arterial pressure was kept constant below control pressure rather than being allowed to rise. The differences in sodium and water excretion were mainly due to the effect of renal arterial pressure on tubular reabsorption. However, the striking increase in sodium and urine excretion which occurred despite the reduction in renal arterial pressure emphasizes the importance of other homoeostatic factors involved in body fluid regulation.