Effect of angiotensin-converting-enzyme inhibition on bradykinin metabolism by vascular endothelial cells

The degradation of bradykinin by angiotensin-converting-enzyme (ACE) activity in cultured human endothelial cells was studied by direct measurement of bradykinin and by its effect on the release of endothelium-derived relaxing factors. The half-life of exogenous bradykinin (10,000 pg/ml) was calculated from the decay of the bradykinin concentration as 46 +/- 2 min in cell monolayers, 133 +/- 15 min in conditioned medium, and 24 +/- 2 min in homogenates. Most of the bradykinin-degrading activity in cell monolayers could be inhibited in a concentration-dependent manner by the ACE inhibitors lisinopril, ramiprilat, and captopril. Bradykinin-degrading activity was released into the culture medium containing one-fourth of the bradykinin-degrading activity found in the presence of cell monolayers. In cell homogenates higher unspecific bradykinin-degrading activities were present. The functional consequence of bradykinin degradation was demonstrated by the potentiating effect of ramiprilat on the generation of endothelium-derived relaxing factors nitric oxide and prostacyclin from endothelial cells. The study supports the concept of increased vasodilatory effects of bradykinin during ACE inhibition.

Download Full-text

ACE-Inhibition and Physical Function: Results From the Trial of Angiotensin-Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors (TRAIN) Study

Journal of the American Medical Directors Association ◽

10.1016/j.jamda.2009.09.014 ◽

2010 ◽

Vol 11 (1) ◽

pp. 26-32 ◽

Cited By ~ 37

Author(s):

Matteo Cesari ◽

Claudio Pedone ◽

Raffaele Antonelli Incalzi ◽

Marco Pahor

Keyword(s):

Risk Factors ◽

Cardiovascular Risk ◽

Angiotensin Converting Enzyme ◽

Cardiovascular Risk Factors ◽

Physical Function ◽

Enzyme Inhibition ◽

Ace Inhibition ◽

Angiotensin Converting Enzyme Inhibition ◽

Converting Enzyme ◽

Converting Enzyme Inhibition

Download Full-text

Angiotensin Converting Enzyme Inhibition Activity of Fennel and Coriander Oils from India

Natural Product Communications ◽

10.1177/1934578x1300800531 ◽

2013 ◽

Vol 8 (5) ◽

pp. 1934578X1300800 ◽

Cited By ~ 2

Author(s):

Sushil Kumar Chaudhary ◽

Niladri Maity ◽

Neelesh Kumar Nema ◽

Santanu Bhadra ◽

Bishnu Pada Saha ◽

...

Keyword(s):

Angiotensin Converting Enzyme ◽

Ace Inhibitor ◽

Radical Scavenging Activity ◽

Radical Scavenging ◽

Ace Inhibition ◽

Angiotensin Converting Enzyme Inhibition ◽

Converting Enzyme ◽

Foeniculum Vulgare ◽

Converting Enzyme Inhibition ◽

Dpph Radical Scavenging

Foeniculum vulgare Mill and Coriandrum sativum L. are very popular spices in Indian kitchens. The present study was an attempt to evaluate the angiotensin converting enzyme (ACE) inhibition and antioxidant activity of the standardized oils of F. vulgare and C. sativum by an UV method using hippuryl-L-histidyl-L-leucine (HHL) as substrate. Standardization of the oils and identification of the chemical-markers (linalool and anethole) present in them was performed through HPLC and GC-MS. Coriander oil showed the higher ACE inhibition with an IC50 value of 34.8 ± 2.3 μg/mL, than fennel oil with an IC50 value of 40.7 ± 3.5 μg/mL. Both oils showed strong DPPH radical scavenging activity. This finding suggests that coriander and fennel oils can be potential leads for the management of hypertension as an ACE inhibitor.

Download Full-text

Acute angiotensin-converting enzyme inhibition evokes bradykinin-induced sympathetic activation in diabetic rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00509.2007 ◽

2007 ◽

Vol 293 (6) ◽

pp. R2260-R2266 ◽

Cited By ~ 3

Author(s):

Robert A. Augustyniak ◽

Maria Maliszewska-Scislo ◽

Haiping Chen ◽

John Fallucca ◽

Noreen F. Rossi

Keyword(s):

Angiotensin Converting Enzyme ◽

Ace Inhibition ◽

Diabetic Rats ◽

Angiotensin Converting Enzyme Inhibition ◽

Converting Enzyme ◽

Sprague Dawley ◽

Renal Sympathetic Nerve Activity ◽

Sprague Dawley Rats ◽

Converting Enzyme Inhibition ◽

Angiotensin Receptor Blockade

We have previously shown that acute intravenous injection of the angiotensin-converting enzyme (ACE) inhibitor enalapril in diabetic rats evokes a baroreflex-independent sympathoexcitatory effect that does not occur with angiotensin receptor blockade alone. As ACE inhibition also blocks bradykinin degradation, we sought to determine whether bradykinin mediated this effect. Experiments were performed in conscious male Sprague-Dawley rats, chronically instrumented to measure mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA), 2 wk after streptozotocin (55 mg/kg iv, diabetic, n = 11) or citrate vehicle (normal, n = 10). Enalapril (2.5 mg/kg iv) decreased MAP in normal rats (−15 ± 3 mmHg), while a smaller response (−4 ± 1 mmHg) occurred in diabetic rats. Despite these different depressor responses to enalapril, HR (+44 ± 8 vs. +26 ± 7 bpm) and RSNA (+90 ± 21 vs +71 ± 8% baseline) increased similarly between the groups ( P ≥ 0.22 for both). Pretreatment with the bradykinin B2 receptor antagonist Hoe 140 (10 μg/kg bolus followed by 0.8·μg−1kg·min−1 infusion) attenuated the decrease in MAP observed with enalapril in normal rats but had no effect in diabetic rats. Moreover, the normal group had smaller HR and RSNA responses (HR: +13 ± 8 bpm; RSNA: +32 ± 13% baseline) that were abolished in the diabetic group (HR: −4 ± 5 bpm; RSNA: −5 ± 9% baseline; P < 0.05 vs. preenalapril values). Additionally, bradykinin (20 μg/kg iv) evoked a larger, more prolonged sympathoexcitatory effect in diabetic compared with normal rats that was further potentiated after treatment with enalapril. We conclude that enhanced bradykinin signaling mediates the baroreflex-independent sympathoexcitatory effect of enalapril in diabetic rats.

Download Full-text

Angiotensin-converting enzyme inhibition increases collateral-dependent muscle blood flow

Journal of Applied Physiology ◽

10.1152/jappl.1993.75.1.452 ◽

1993 ◽

Vol 75 (1) ◽

pp. 452-457 ◽

Cited By ~ 28

Author(s):

H. T. Yang ◽

R. L. Terjung

Keyword(s):

Blood Flow ◽

Angiotensin Converting Enzyme ◽

Muscle Blood Flow ◽

Ace Inhibition ◽

Angiotensin Converting Enzyme Inhibition ◽

High Dose ◽

Converting Enzyme ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Converting Enzyme Inhibition

The purpose of this study was to evaluate the effect of angiotensin-converting enzyme (ACE) inhibition on collateral-dependent blood flow (BF) during exercise. Adult male Sprague-Dawley rats (approximately 320 g) were fed zabicipril, an ACE inhibitor, mixed with powdered food at 0.0, 0.3, and 3.0 mg.kg-1 x day-1 (n = 12/group) for 5–7 days. Under ketamine-acepromazine anesthesia, the carotid and caudal arteries were catheterized for BF determination, and both femoral arteries were ligated to remove the primary route for BF to the distal limb tissue. Later on the same day, collateral-dependent hindlimb BF was determined at two treadmill speeds (15 and 25 m/min at 15% grade) with 85Sr- and 141Ce-labeled 15-microns microspheres. Zabicipril ingestion induced 50 and 65% inhibition of plasma ACE activity in the low- and high-dose group, respectively (P < 0.001). ACE inhibition did not affect body weight, blood pressure, or heart rate of the rats during exercise. However, BFs to the total hindlimb were 44 and 36% higher (P < 0.001) in zabicipril-treated animals than in the zero-dose controls (approximately 45 ml.min-1 x 100 g-1). Furthermore, BFs to the proximal hindlimb, distal hindlimb, and gastrocnemius-plantaris-soleus group were 33–44% greater in drug-treated than in control animals (P < 0.025). Higher speed (25 m/min) failed to further increase muscle BF; therefore peak BFs were likely achieved. These results indicate that collateral-dependent BF was improved by ACE inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Download Full-text