Potential Cardioprotective Effect of Mibefradil in the Long-Term Treatment of Hypertension

Waeber, Bernard

doi:10.1159/000047275

Cited by 3 publications

(3 citation statements)

References 33 publications

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“…In patch‐clamp studies in native cells from guinea‐pig azygous vein, mibefradil has approximately 30‐fold selectivity of T‐ over L‐type calcium channels 11 . However, it is important to note that mibefradil has not been reported to cause major orthostatic side‐effects, at least with oral administration, in patients in various studies 45–47 . Therefore, the clinical relevance of our finding in conscious rabbits requires further investigation.…”

Section: Discussionmentioning

confidence: 82%

Acute Effects Of L‐ And T‐Type Calcium Channel Antagonists On Cardiovascular Reflexes In Conscious Rabbits

Devlin

Angus

Wilson

et al. 2002

Clin Exp Pharma Physio

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1. The effects of the relatively selective T-type voltage- operated calcium channel (VOCC) antagonist mibefradil were compared with verapamil, an L-type VOCC antagonist, on a range of autonomic reflexes in conscious rabbits. 2. Mean arterial pressure (MAP), heart rate (HR), the baroreceptor-HR reflex, postural adaptation reflex (90 degrees head-up tilt), Bezold-Jarisch-like reflex and the vasoconstrictor component of the nasopharyngeal reflex were assessed before and during i.v. infusion of vehicle (saline), mibefradil or verapamil. Doses of mibefradil that gave low (M1; 0.45 +/- 0.02 microg/mL) and high (M2; 0.93 +/- 0.05 microg/mL) plasma concentrations, or verapamil (0.059 +/- 0.004 microg/mL; n = 6 each) were chosen to mimic clinically observed therapeutic levels. 3. At steady state infusion over 30-90 min, MAP was significantly lower in M2 (- 7 mmHg) and verapamil (- 6 mm Hg) treatments, but only verapamil caused a significant tachycardia (+ 31 b.p.m.) compared with vehicle. Mibefradil (M2) and verapamil decreased the HR range of the baroreflex by 27 and 29%, respectively, but neither treatment affected the vagal or sympathetic constrictor components of the Bezold-Jarisch-like and nasopharyngeal reflexes, respectively. 4. In response to 90 degrees tilt, vehicle- and verapamil-treated rabbits responded with small rises in MAP of 4 +/- 2 and 8 +/- 2 mm Hg, respectively, 5 s into the upright posture, while M1 and M2 caused falls in MAP of 6 +/- 4 and 9 +/- 3 mm Hg, respectively, at 5 s. 5. Thus, both L- and T-type VOCC antagonists, at plasma concentrations in the clinical range, lowered MAP in the conscious rabbit, but only mibefradil caused postural hypotension. We conclude that T-type VOCC may play an important role in the venoconstrictor reflex in response to tilt in the rabbit.

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Section: Discussionmentioning

confidence: 82%

Acute Effects Of L‐ And T‐Type Calcium Channel Antagonists On Cardiovascular Reflexes In Conscious Rabbits

Devlin

Angus

Wilson

et al. 2002

Clin Exp Pharma Physio

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“…Conversely, there are also reports demonstrating a safety of long-term antihypertensive therapy with nifedipine, 17) a beneficial effect of calcium antagonists on fatal myocardial infarction, 18) a potential cardioprotective effect of a new type of calcium antagonist, 19) and a preventive effect against cardiovascular complications among elderly patients with isolated systolic hypertension who were treated with nitrendipine as a starting antihypertensives agent. 20) The Hypertension Optimal Treatment (HOT) Study Group 21) used the long acting calcium antagonist felodipine as a basic antihypertensive agent and reported beneficial results.…”

Section: (58%)mentioning

confidence: 99%

Difference in the Occurrence of Cardiovascular Events According to Class of Antihypertensive Agent, Based on a Follow-Up Study of Japanese Hypertension Patients.

et al. 2001

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SUMMARYWe conducted a nested case-control study to evaluate the relationship between antihypertensive agent class and the incidence of initial cardiovascular events. A total of 7,443 patients being treated with an antihypertensive agent in 1985-1986 were enrolled for follow-up of up to 5 years. A total of 362 patients (186 males and 176 females) developed cardiovascular events. Age (5-year interval) and sex-matched controls were then randomly selected. A multiple logistic regression analysis was done to control for the effects of confounding factors. The results showed that the use of diuretics and β-blockers was associated with a reduced risk of cardiovascular events (odds ratio [OR] =0.65, 95% confidence interval [CI]: 0.49-0.86, and OR=0.75, 95% CI: 0.56-1.02, respectively), against a significantly raised risk associated with the use of calcium antagonists (OR=1.34, 95% CI: 1.03-1.80). However, as far as stroke was concerned, there was no significant association of risk with the use of any agent. The control group was found to be similar to the case group with respect to the changes in the treatment program during the follow-up period. The results suggest that the calcium antagonists used in Japan during the period of 1985-1990 constituted a potential risk for the occurrence of cardiovascular events. (Jpn Heart J 2001; 42: 585-595)

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“…Studies also reported ARBs to be superior in ameliorating endothelial function and vascular damage [ 19 – 21 ]. Despite of their wide usage as first-line therapy, the cardiovascular protective effects of these agents still remained elusive [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Allisartan ameliorates vascular remodeling through regulation of voltage-gated potassium channels in hypertensive rats

Zhang

Zhao

et al. 2021

BMC Pharmacol Toxicol

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Background The objective of the present study was to determine the effect of allisartan, a new angiotensin II type 1 receptor antagonist on vascular remodeling through voltage gated potassium channels (Kv7) in hypertensive rats. Methods The study included a total of 47 Sprague Dawley (SD) rats. The animals were randomized to sham operation (n = 14), untreated hypertensive control group (n = 18) and allisartan treatment group (n = 15). Using renal artery stenosis, hypertension was induced in animals. Single dose of allisartan was administered intra-gastrically to animals in the allisartan treatment group and match placebo in the other 2 groups. Wire myography was used to measure the muscle tension in isolated mesenteric arteries from the animals. Real-time polymerase chain reaction was used to quantify the expression of Kv7 channel mRNA subunits. Results After 4 weeks of treatment, a significant decrease in mean arterial, systolic and diastolic blood pressure (SBP and DBP) was observed in allisartan treatment group compared to hypertension control group. The median arterial wall thickness and area/diameter ratio reduced significantly in treatment group compared to untreated hypertension group (P < 0.05). Wire myography demonstrated increased relaxation of mesenteric artery with increase in concentration of ML213. A significant up-regulation in the expression of all Kv7 mRNA subunits was observed in allisartan group compared to untreated hypertension group. Conclusions From the results, allisartan was found to lower BP and preserve vascular remodeling through Kv7 channels.

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Potential Cardioprotective Effect of Mibefradil in the Long-Term Treatment of Hypertension

Cited by 3 publications

References 33 publications

Acute Effects Of L‐ And T‐Type Calcium Channel Antagonists On Cardiovascular Reflexes In Conscious Rabbits

Acute Effects Of L‐ And T‐Type Calcium Channel Antagonists On Cardiovascular Reflexes In Conscious Rabbits

Difference in the Occurrence of Cardiovascular Events According to Class of Antihypertensive Agent, Based on a Follow-Up Study of Japanese Hypertension Patients.

Allisartan ameliorates vascular remodeling through regulation of voltage-gated potassium channels in hypertensive rats

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