Direct effects in vivo of angiotensins I and II on the canine sinus node

1991 ◽  
Vol 69 (3) ◽  
pp. 389-392 ◽  
Author(s):  
C. Lambert ◽  
D. Godin ◽  
P. Fortier ◽  
R. Nadeau
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Angiotensin Ii ◽  
Sinus Node ◽  
Converting Enzyme ◽  
Chronotropic Effect ◽  
Angiotensin I ◽  
Sinus Node Artery ◽  
Blood Pressures

The chronotropic responses to angiotensins I and II (5 μg in 1 mL Tyrode's solution) injected into the sinus node artery were assessed before and after the intravenous administration of captopril (2 mg/kg) and saralasin (20 μg/kg) in anaesthetized dogs. The effects of angiotensin II given intravenously were also observed. The animals (n = 8) were vagotomized and pretreated with propranolol (1 mg/kg, i.v.) to prevent baroreceptor-mediated responses to increases in blood pressure. Injection of angiotensin I into the sinus node artery induced significant increases in heart rate (114 ± 6 vs. 133 ± 6 beats/min) and in systemic systolic (134 ± 13 vs. 157 ± 14 mmHg; 1 mmHg = 133.3 Pa) and diastolic (95 ± 10 vs. 126 ± 13 mmHg) blood pressures. Similar results were obtained when angiotensin II was injected into the sinus node artery, but intravenous injection induced changes in systolic (138 ± 8 vs. 180 ± 25 mmHg) and diastolic (103 ± 8 vs. 145 ± 20 mmHg) blood pressures only. Captopril induced a significant decrease in systolic (118 ± 11 vs. 88 ± 12 mmHg) and diastolic (84 ± 9 vs. 59 ± 9 mmHg) blood pressures without affecting the heart rate (109 ± 6 vs. 106 ± 6 beats/min). Saralasin produced a significant increase in systolic (109 ± 7 vs. 126 ± 12 mmHg) blood pressure only. Increments in heart rate and systolic and diastolic blood pressures in response to angiotensins I and II were, respectively, abolished by captopril and saralasin. It was concluded that angiotensin II has, in vivo, a direct positive chronotropic effect that can be blocked by saralasin. The antagonism by captopril of the response to angiotensin I suggests the presence of local tissue converting enzyme activity in the region of the sinus node.Key words: angiotensin, chronotropic effect, tissue converting enzyme.

In vivo B2-receptor-mediated negative chronotropic effect of bradykinin in canine sinus node

1993 ◽  
Vol 265 (3) ◽  
pp. H876-H879 ◽  
Author(s):  
C. Ribuot ◽  
D. Godin ◽  
R. Couture ◽  
D. Regoli ◽  
R. Nadeau
Keyword(s):  
Heart Rate ◽  
Enzyme Inhibition ◽  
Sinus Node ◽  
Converting Enzyme ◽  
Chronotropic Effect ◽  
Chronotropic Response ◽  
Negative Chronotropic Effect ◽  
Blood Pressures ◽  
Converting Enzyme Inhibition

The chronotropic response to bradykinin (BK) injected into the sinus node artery was evaluated in anesthetized dogs. The animals (n = 14) were vagotomized and pretreated with propranolol (1 mg/kg i.v.) to prevent baroreceptor-mediated effects. Dose-dependent decreases in heart rate (from 2.4 +/- 1.3% for 1 microgram of BK to 13.1 +/- 3.7% for 10 micrograms of BK), as well as a significant fall in systemic systolic and diastolic blood pressures, were observed. Captopril (2 mg/kg i.v.) caused significant decreases in systolic (from 117 +/- 11 to 77 +/- 12 mmHg, P < 0.001) and diastolic (from 87 +/- 8 to 52 +/- 8 mmHg, P < 0.001) blood pressures but had no effect on heart rate. Converting-enzyme inhibition potentiated the BK-induced bradycardia. The new potent B2-receptor antagonist, HOE 140 (100 micrograms), significantly blocked the BK-induced chronotropic effect, whereas desArg9-BK, a B1-receptor agonist, was without effect. Prostaglandin involvement was excluded, since pretreatment with indomethacin did not prevent the bradycardia. In conclusion, in vivo BK induces a direct negative chronotropic effect, which is potentiated by converting-enzyme inhibition and is mediated by the B2-receptors independently of the prostaglandins.

Effect of enalapril (MK-421), an orally active angiotensin I converting enzyme inhibitor, on blood pressure, active and inactive plasma renin, urinary prostaglandin E2, and kallikrein excretion in conscious rats

1984 ◽  
Vol 62 (1) ◽  
pp. 116-123 ◽  
Author(s):  
Ernesto L. Schiffrin ◽  
Jolanta Gutkowska ◽  
Gaétan Thibault ◽  
Jacques Genest
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Plasma Renin Activity ◽  
Plasma Renin ◽  
Ace Inhibition ◽  
Renin Activity ◽  
Prostaglandin E ◽  
Converting Enzyme ◽  
Angiotensin I ◽  
Angiotensin I Converting Enzyme

The angiotensin I converting enzyme (ACE) inhibitor enalapril (MK-421), at a dose of 1 mg/kg or more by gavage twice daily, effectively inhibited the pressor response to angiotensin I for more than 12 h and less than 24 h. Plasma renin activity (PRA) did not change after 2 or 4 days of treatment at 1 mg/kg twice daily despite effective ACE inhibition, whereas it rose significantly at 10 mg/kg twice daily. Blood pressure fell significantly and heart rate increased in rats treated with 10 mg/kg of enalapril twice daily, a response which was abolished by concomitant angiotensin II infusion. However, infusion of angiotensin II did not prevent the rise in plasma renin. Enalapril treatment did not change urinary immunorcactive prostaglandin E2 (PGE2) excretion and indomethacin did not modify plasma renin activity of enalapril-treated rats. Propranolol significantly reduced the rise in plasma renin in rats receiving enalapril. None of these findings could be explained by changes in the ratio of active and inactive renin. Water diuresis, without natriuresis and with a decrease in potassium urinary excretion, occurred with the higher dose of enalapril. Enalapril did not potentiate the elevation of PRA in two-kidney one-clip Goldblatt hypertensive rats. In conclusion, enalapril produced renin secretion, which was in part β-adrenergically mediated. The negative short feedback loop of angiotensin II and prostaglandins did not appear to be involved. A vasodilator effect, apparently independent of ACE inhibition, was found in intact conscious sodium-replete rats.

Inactivation of Bradykinin and Angiotensin I Conversion in Conscious Rats with Two-Kidney, One-Clip Hypertension

1982 ◽  
Vol 63 (s8) ◽  
pp. 199s-201s ◽  
Author(s):  
Inge E. K. Trindade ◽  
Eduardo M. Krieger
Keyword(s):  
Enzyme Activity ◽  
Angiotensin Ii ◽  
Mean Arterial Pressure ◽  
Renal Artery ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Hypertensive Rats ◽  
Angiotensin I ◽  
Parallel Increase

1. The extents of pulmonary degradation of bradykinin (BK) and angiotensin I (ANG I) to angiotensin II (ANG II) conversion were measured simultaneously to determine whether converting enzyme activity, in vivo, is altered in two-kidney, one-clip hypertensive rats (15, 60 and 180 days after renal artery clipping). 2. Inactivation of BK (estimated by comparing equipressor doses injected intravenously and intra-aortically) was markedly increased in these hypertensive rats: 98.5% (15 days), 98.4% (60 days) and 99.5% (180 days) vs 95.6% in control rats. All groups of hypertensive rats exhibited hyper-reactivity to intra-aortic BK, requiring doses 14–38 times smaller than the control rats to produce the same depressor response. 3. The percentage of ANG I conversion (calculated from equipressor doses of ANG I and ANG II injected intravenously) was elevated after 15 days (46.0% vs 28.1% in control rats), unchanged after 60 days (27.7%) and slightly elevated after 180 days (36.0%). Hyporeactivity to ANG II was observed 15 and 180 days after renal artery clipping (doses six times were needed to produce a standard increase in mean arterial pressure). No alterations were found in the rats at 60 days after artery clipping. 4. The increased degradation of BK cannot be explained solely by elevation of converting enzyme activity since no parallel increase in ANG I conversion was observed, indicating that other bradykininases in the lung may be involved.

Angiotensin I conversion and vascular reactivity in pathophysiological states in dogs

1980 ◽  
Vol 48 (2) ◽  
pp. 308-312 ◽  
Author(s):  
P. J. Leuenberger ◽  
S. A. Stalcup ◽  
L. M. Greenbaum ◽  
R. B. Mellins ◽  
G. M. Turino
Keyword(s):  
Blood Pressure ◽  
Enzyme Activity ◽  
Angiotensin Ii ◽  
Vascular Reactivity ◽  
Blood Pressure Response ◽  
Acute Hypoxia ◽  
Pressure Response ◽  
Converting Enzyme ◽  
Angiotensin I ◽  
Arterial Blood

To determine if angiotension converting enzyme activity is altered by acute pathophysiological insults, we assessed angiotensin I conversion using a blood pressure response technique in anesthetized dogs studied during acute 100% O2 breathing and acute acid-base derangements. Also, we determined systemic vascular reactivity to angiotensin II by measuring the magnitude and duration of the arterial blood pressure response to intra-arterial injections of angiotensin II under these same conditions. Angiotensin I conversion found in normoxia [91 +/- 7 (SD)%] was unchanged by acute acidosis, alkalosis, and hyperoxia. During acute hyperoxia the mean half time of the hypertensive response increased from 68 +/- 25 (SD) s at a PaO2 of 112 +/- 18 (SD) Torr to 100 +/- 34 (SD) s at a PaO2 of 491 +/- 47 (SD) Torr (P less than 0.01). No other pathophysiological condition studied had any effect on reactivity of systemic vasculature to angiotensin II. We conclude that, except during acute hypoxia as previously shown, converting enzyme activity is resistant to other pathophysiological insults and that vascular responsiveness to angiotensin II is enhanced by hyperoxia.

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

1980 ◽  
Vol 58 (6) ◽  
pp. 445-450 ◽  
Author(s):  
J. J. Morton ◽  
M. Tree ◽  
J. Casals-Stenzel
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Fold Increase ◽  
Converting Enzyme ◽  
Angiotensin I ◽  
Active Inhibitor ◽  
Arterial Blood ◽  
Rapid Fall ◽  
Angiotensin Iii ◽  
Plasma Angiotensin

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 μg 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 μg h−1 kg−1 (mean pre-infusion value for all samples was 39 ± sd 15 pmol/I, 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 μg 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)

Comparative Pharmacology of New Specific Angiotensin Antagonists

1974 ◽  
Vol 48 (s2) ◽  
pp. 19s-21s
Author(s):  
B. A. Schoelkens
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Blood Pressure Response ◽  
Renal Hypertension ◽  
Antagonistic Activity ◽  
Conscious Rats ◽  
Blood Pressures ◽  
Colon Ascendens

1. The angiotensin II antagonism by newly synthesized 8-C-phenylglycine analogues of [5-isoleucine]angiotensin II in different preparations was investigated in vitro and in vivo. 2. All analogues competitively inhibited the myotropic effect of angiotensin II on the isolated colon ascendens of the guinea-pig and the stomach of the rat. 3. In normotensive dogs, cats, rabbits, guinea-pigs and rats the blood pressure response to infused angiotensin II was inhibited by the antagonists. The angiotensin II-induced fall in renal blood flow in the dog was blocked during infusion of the analogues. Acute renal hypertension in rats was significantly decreased. Of conscious rats variously with normal blood pressures, spontaneous hypertension and chronic renal hypertension, only in the last group could a marked uniform fall in blood pressure be demonstrated. The central pressor effect of angiotensin II was also inhibited in conscious rats. 4. 8-C-Phenylglycine analogues of [5-isoleucine]-angiotensin II exhibit a specific antagonistic activity to endogenous and exogenous angiotensin II.

Functional role of local angiotensin-converting enzyme (ACE) in adrenal catecholamine secretion in vivo

1999 ◽  
Vol 77 (11) ◽  
pp. 878-885 ◽  
Author(s):  
Nobuharu Yamaguchi ◽  
Daniel Martineau ◽  
Stéphane Lamouche ◽  
Richard Briand
Keyword(s):  
Angiotensin Ii ◽  
Adrenal Gland ◽  
Angiotensin Converting Enzyme ◽  
Venous Blood Flow ◽  
Dependent Manner ◽  
Converting Enzyme ◽  
Left Adrenal Gland ◽  
Angiotensin I ◽  
Aortic Blood

The aim of the present study was to investigate whether exogenous angiotensin I (AngI) is locally converted to angiotensin II (AngII), which in turn results in an increase in the adrenal catecholamine (CA) secretion in the adrenal gland in anesthetized dogs. Plasma CA concentrations in adrenal venous and aortic blood were determined by an HPLC-electrochemical method. Adrenal venous blood flow was measured by gravimetry. Local administration of AngI (0.0062 to 6.2 µg, 0.0096 to 9.6 µM) to the left adrenal gland resulted in significant increases in CA output in a dose-dependent manner. Following administration of 0.62 µg (0.96 µM) of AngI, adrenal epinephrine and norepinephrine outputs increased from 20.8 ± 13.6 to 250.9 ± 96.4 ng·min-1·g-1 (p < 0.05, n = 5) and from 2.8 ± 1.7 to 29.6 ± 11.1 ng·min-1·g-1 (p < 0.05, n = 5), respectively. From the same left adrenal gland, the output of AngII increased from -0.02 ± 0.04 to 26.39 ± 11.38 ng·min-1·g-1 (p < 0.05, n = 5), while plasma concentrations of AngII in aortic blood remained unchanged. In dogs receiving captopril (12.5 µg, 0.5 mM) 10 min prior to AngI, the net amounts of CA and AngII secreted during the first 3 min after AngI were diminished by about 80% (p < 0.05, n = 5) compared with those obtained from the control group. There was a close correlation (r2 = 0.91, n = 6) between the net increases in AngII and CA outputs induced by AngI. The results indicate that the local angiotensin converting enzyme is functionally involved in regional AngII formation in the canine adrenal gland in vivo. The study suggests that AngII thus generated may play a role in the local regulation of adrenal CA secretion.Key words: angiotensin I, angiotensin II, captopril, adrenal gland, anesthetized dog.

Pressor Response to Angiotensin I and Angiotensin II: The Site of Conversion of Angiotensin I

1972 ◽  
Vol 43 (6) ◽  
pp. 839-849 ◽  
Author(s):  
E. C. Osborn ◽  
G. Tildesley ◽  
P. T. Pickens
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Pressor Response ◽  
Left Ventricular ◽  
Angiotensin I ◽  
Intravenous Injections ◽  
Pressor Responses ◽  
The Difference

1. The pressor responses to angiotensin I were compared with those to angiotensin II after injections into the left ventricle and jugular vein in the sheep, dog and pig. 2. The ability of angiotensin I to raise the blood pressure was less than that of angiotensin II with both routes of injection, a difference which was more marked after ventricular injection. 3. When equipressor doses of the hormones were given there was a delay of 1–3 s in the onset of the pressor response to angiotensin I compared with angiotensin II after left-ventricular injections; the difference in the delay in onset was less apparent with intravenous injections. 4. The development of the pressor responses was similar with both hormones when equipressor doses were used but the rises in blood pressure were more prolonged with angiotensin I, especially when given by the left-ventricular route. 5. The in vitro rate of activation of angiotensin I by blood was much slower than the apparent in vivo formation of angiotensin II.

scholarly journals Bioavailability of angiotensin I converting enzyme inhibitory peptides

2004 ◽  
Vol 92 (3) ◽  
pp. 357-366 ◽  
Author(s):  
Vanessa Vermeirssen ◽  
John Van Camp ◽  
Willy Verstraete
Keyword(s):  
Blood Pressure ◽  
Antihypertensive Effect ◽  
Converting Enzyme ◽  
Angiotensin I ◽  
Inhibitory Peptides ◽  
Angiotensin I Converting Enzyme ◽  
Ace Inhibitory Peptides ◽  
Ace Inhibitory

Hypertension or high blood pressure is a significant health problem worldwide. Bioactive peptides that inhibit angiotensin I converting enzyme (ACE) in the cardiovascular system can contribute to the prevention and treatment of hypertension. These ACE inhibitory peptides are derived from many food proteins, especially milk proteins. An ACE inhibitory activity in vitro does not always imply an antihypertensive effect in vivo. Even if it does, it is very difficult to establish a direct relationship between in vitro and in vivo activity. This is mainly due to the bioavailability of the ACE inhibitory peptides after oral administration and the fact that peptides may influence blood pressure by mechanisms other than ACE inhibition. To exert an antihypertensive effect after oral ingestion, ACE inhibitory peptides have to reach the cardiovascular system in an active form. Therefore, they need to remain active during digestion by human proteases and be transported through the intestinal wall into the blood. The bioavailability of some ACE inhibitory peptides has been studied. It is also known that (hydroxy)proline-containing peptides are generally resistant to degradation by digestive enzymes. Peptides can be absorbed intact through the intestine by paracellular and transcellular routes, but the potency of the bioactivity after absorption is inversely correlated to chain length. In addition, some strategies are proposed to increase the bioavailability of ACE inhibitory peptides. Further research into the bioavailability of ACE inhibitory peptides will lead to the development of more effective ACE inhibitory peptides and foods.

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