scholarly journals Angiotensin II effects on ischemic focal ventricular tachycardia are predominantly mediated through myocardial AT2 receptor

2009 ◽  
Vol 297 (5) ◽  
pp. H1889-H1898 ◽  
Author(s):  
Rakesh Gopinathannair ◽  
Ashok K. Chaudhary ◽  
Dezhi Xing ◽  
Debra Ely ◽  
Wei Zheng ◽  
...  
Keyword(s):  
Ventricular Tachycardia ◽  
Angiotensin Ii ◽  
Enzyme Inhibitors ◽  
Three Dimensional ◽  
Coronary Artery Occlusion ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Artery Occlusion ◽  
Converting Enzyme Inhibitors ◽  
Triggered Activity

Ischemic focal ventricular tachycardia (VT) occurs in animals and humans. Angiotensin-converting enzyme inhibitors and receptor blockers reduce sudden death in patients with ischemic heart disease. In our dog model of coronary artery occlusion (CAO), we tested the hypothesis that angiotensin II (AGII) will selectively promote focal VT and that the specific AT2 blocker PD-123319 (PD), or AT1 blocker losartan, will affect this VT. Anesthetized dogs ( n = 90) underwent CAO, followed by three-dimensional activation mapping of inducible VT. Dogs without VT in 1–3 h after CAO received AGII, and those with VT received either PD or losartan. Focal endocardium excised from ischemic sites was studied in vitro with standard microelectrode. Of 33 dogs with no inducible VT, AGII infusion resulted in sustained VT of only focal Purkinje origin in 13 (39%) compared with 0 of 20 dogs with saline. Of 26 dogs with inducible VT at baseline, given PD, reinduction was blocked in 8 of 10 ( P < 0.05) focal VT, but only 1 of 15 with reentry. In contrast, of 11 dogs given losartan, reinduction of either mechanism was not blocked. In vitro triggered activity in Purkinje was blocked by PD in 13 of 19 ( P < 0.05), but not by losartan in 8. Also, triggered activity was promoted by AGII, losartan, or the combination in 9 of 12 tissues. AGII promotes only focal, mainly Purkinje ischemic VT. PD, but not losartan, preferentially blocked focal VT, which is likely due to triggered activity due to delayed afterdepolarizations in Purkinje.

Pharmacological stimulation of cardiac gap junction coupling does not affect ischemia-induced focal ventricular tachycardia or triggered activity in dogs

2005 ◽  
Vol 288 (2) ◽  
pp. H511-H516 ◽  
Author(s):  
Dezhi Xing ◽  
Anne Louise Kjølbye ◽  
Jørgen S. Petersen ◽  
James B. Martins
Keyword(s):  
Ventricular Tachycardia ◽  
Gap Junction ◽  
Plasma Concentrations ◽  
Three Dimensional ◽  
In Vitro Study ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Triggered Activity

The role of gap junction intercellular communication (GJIC) in ischemia-induced focal ventricular tachycardia (VT) is unknown. We have developed a new, stable antiarrhythmic peptide analog named ZP123 that selectively increases GJIC and prevents reentrant VT. Our aim in this study was to use ZP123 as a tool to assess the role of GJIC on occurrence of ischemia-induced focal VT and triggered activity (TA) due to delayed afterdepolarizations (DADs). Focal VT was induced by programmed stimulation in α-chloralose-anesthetized, open-chest dogs 1–4 h after coronary artery occlusion. Three-dimensional activation mapping was done using 6 bipolar electrograms on each of 23 multipolar needles in the risk zone. Dogs were randomly assigned to receive either saline or ZP123 cumulatively at three dose levels (an intravenous bolus followed by a 30-min infusion per dose). Attempts to induce VT were repeated in each dose. Mass spectrometry was used to measure plasma ZP123 concentrations. Standard microelectrode techniques were used for in vitro study of DADs and TA. Twenty-six dogs with focal VT were included. ZP123 did not affect the inducibility of focal VT at any plasma concentrations vs. saline (0.8 ± 0.1 nM, 77 vs. 75%; 7.8 ± 0.4 nM, 86 vs. 77%; and 78.8 ± 5.0 nM, 77 vs. 91%). In vitro, ZP123 did not affect the induction of DADs (12/12) and TAs (10/10) in ischemic tissues or tissue removed from the origin of focal VT (DADs, 8/8; TAs, 4/4). Therefore, although indirect, the data with the doses and concentrations used suggest that GJIC may not play a major role in the genesis of focal activity in the ischemic models studied.

scholarly journals Suppression of Aldosterone Synthesis and Secretion by Channel Antagonists

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Keiichi Ikeda ◽  
Tsuyoshi Isaka ◽  
Kouki Fujioka ◽  
Yoshinobu Manome ◽  
Katsuyoshi Tojo
Keyword(s):  
Angiotensin Ii ◽  
Enzyme Inhibitors ◽  
Renin Angiotensin System ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Channel Blockers ◽  
Converting Enzyme Inhibitors ◽  
Renin Angiotensin ◽  
Aldosterone Production ◽  
Ras Inhibitors

Aldosterone, a specific mineralocorticoid receptor (MR) agonist and a key player in the development of hypertension, is synthesized as a final product of renin-angiotensin-aldosterone system. Hypertension can be generally treated by negating the effects of angiotensin II through the use of angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin II type 1 receptor antagonists (ARBs). However, the efficacy of angiotensin II blockade by such drugs is sometimes diminished by the so-called “aldosterone breakthrough” effect, by which ACE-Is or ARBs (renin-angiotensin system (RAS) inhibitors) gradually lose their effectiveness against hypertension due to the overproduction of aldosterone, known as primary aldosteronism. Although MR antagonists are used to antagonize the effects of aldosterone, these drugs may, however, give rise to life-threatening adverse actions, such as hyperkalemia, particularly when used in conjunction with RAS inhibitors. Recently, several groups have reported that some dihydropyridine Ca2+channel blockers (CCBs) have inhibitory actions on aldosterone production inin vitroand in the clinical setting. Therefore, the use of such dihydropyridine CCBs to treat aldosterone-related hypertension may prove beneficial to circumvent such therapeutic problems. In this paper, we discuss the mechanism of action of CCBs on aldosterone production and clinical perspectives for CCB use to inhibit MR activity in hypertensive patients.

Overdrive pacing of early ischemic ventricular tachycardia: evidence for both reentry and triggered activity

2005 ◽  
Vol 288 (3) ◽  
pp. H1124-H1130 ◽  
Author(s):  
David O. Arnar ◽  
Dezhi Xing ◽  
James B. Martins
Keyword(s):  
Ventricular Tachycardia ◽  
Cycle Length ◽  
Three Dimensional ◽  
Coronary Artery Occlusion ◽  
Canine Model ◽  
Artery Occlusion ◽  
Triggered Activity ◽  
Three Dimensional Mapping ◽  
Cycle Lengths ◽  
Overdrive Pacing

Entrainment can be a useful method to identify reentry as a mechanism of ventricular tachycardia (VT). In this study, we evaluated the effect of gradually decreasing cycle lengths of overdrive pacing for stable VT induced in a canine model 1–3 h after coronary occlusion. Intact dogs underwent anterior descending coronary artery occlusion after instrumentation of the risk zone with 21 multipolar plunge needles, each recording 6 bipolar electrograms. Overdrive pacing was attempted if the animals had sustained hemodynamically stable VT, looking for evidence of entrainment. Subsequent three-dimensional mapping determined the mechanism of VT. Fifteen of the 21 dogs studied demonstrated entrainment with overdrive pacing by progressive QRS fusion alone ( 1 ), the first nonpaced QRS entrained to the paced cycle length only ( 7 ), or both ( 7 ). Five of these 15 dogs also had postpacing acceleration of the VT at a subsequent faster pacing cycle length. The mechanism of acceleration in four was a change to a VT with a focal origin. The prepacing mechanism in all 15 dogs was subsequently mapped to reentry. Regarding the six VTs, which demonstrated no evidence for entrainment, the site of earliest activity was mapped to a focal origin in all. These data showing entrainment of inducible reentrant VTs and lack of such for focal VTs support that the focal VTs seen in this study are unlikely the result of microreentry but possibly a mechanism as triggered activity.

Comparative effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on pulmonary function in hypertensive patients

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Azza S. Jabbar ◽  
Nadheera F. Neamah ◽  
Ahmed H. Al-Darraji
Keyword(s):  
Angiotensin Ii ◽  
Adverse Effects ◽  
Angiotensin Converting Enzyme ◽  
Enzyme Inhibitors ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Converting Enzyme ◽  
Angiotensin Ii Receptor ◽  
Converting Enzyme Inhibitors ◽  
Hypertensive Patients ◽  
Receptor Blockers

Abstract Objectives Hypertension is a very common cardiovascular disease. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) are widely used to treat hypertension. Many patients with hypertension are vulnerable to the antihypertensive adverse effects, which potentially reduces the adherence rate. Therefore, we conducted this study in order to evaluate the safety profile of both classes (ACEi and ARBs) on respiratory functions. Methods Two main groups of subjects were studied: first group is healthy control subjects and the second group is hypertensive patients, which was subdivided into subgroups in order to investigate the effect of all tested medications (captopril, enalapril, lisinopril, losartan, and valsartan). Respiratory efficiency was evaluated by measuring pulmonary function tests: FEV1, FVC, and FEV1%. Measurements were done using micromedical spirometer. Results We found that ARBs do not impair normal respiratory functions as measured by FEV1, FEV1%, and FVC in hypertensive patients. While ACEi treatments significantly reduced FEV1, FEV1%, and FVC compared to the other groups. Conclusions ARBs are not associated with any harmful effects on respiratory functions in hypertensive patients, unlike ACEi. As such, they could represent a first-choice treatment for hypertensive patients who are at high risk to the respiratory adverse effects.

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