Effects of Nicardipine on Coronary, Vertebral and Renal Arterial Flows in Patients with Essential Hypertension.

Suzuki, Shoji; Ohtsuka, Sadanori; Ishikawa, Kimito; Yamaguchi, Iwao

doi:10.1291/hypres.26.193

Cited by 11 publications

(6 citation statements)

References 48 publications

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“…It has also been reported that an ARB reduced vascular microinflammation in essential hypertension (27). However, a CCB was shown to increase basal coronary flow but not hyperemic coronary flow and resulted in reduced CFVR (28). Thus, these previous findings suggest that ARBs and CCBs have quite different effects on CFVR, in agreement with the present study.…”

Section: Changes Of Cfvr By Arbsupporting

confidence: 92%

Angiotensin Receptor Blocker Improves Coronary Flow Velocity Reserve in Hypertensive Patients: Comparison with Calcium Channel Blocker

et al. 2007

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Large-scale clinical studies have indicated that angiotensin receptor blockers (ARBs) have beneficial effects against cardiovascular diseases. We designed this study to compare the effects of an ARB and a calcium channel blocker (CCB) on coronary flow velocity reserve (CFVR), a predictor of cardiovascular events, as estimated using transthoracic Doppler echocardiography. Sixteen hypertensive patients (63.1+/-9.6 years old; 10 males) were randomly allocated in a double-blind fashion to valsartan (n=8, 40-80 mg/day) or nifedipine (n=8, 20-40 mg/day) groups. Age- and gender-matched subjects without hypertension were enrolled as a control group (n=12). CFVR was calculated by dividing the adenosine triphosphate-induced hyperemic flow velocity by the basal flow velocity in the left anterior descending coronary artery. Baseline characteristics and reduction in systolic and diastolic blood pressure after 6 months were similar in both groups. CFVR in the valsartan group increased from 2.34+/-0.38 to 3.10+/-0.84 at 2 months (p<0.05), and to 3.04+/-1.09 at 6 months (p<0.01). Both values became comparable to that in the control group (2.81+/-0.60). CFVR in the valsartan group was significantly higher (p<0.001) than that in the nifedipine group, which was little changed at 6 months. This discrepancy was derived from the significant increase of hyperemic velocity in the valsartan group, from 36.6+/-17.3 cm/s to 41.1+/-12.7 cm/s at 2 months, and to 48.1+/-20.2 cm/s at 6 months. We concluded that the ARB valsartan not only reduced high blood pressure but improved CFVR in hypertensive patients. However, these effects were not seen with the CCB nifedipine.

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Section: Changes Of Cfvr By Arbsupporting

confidence: 92%

Angiotensin Receptor Blocker Improves Coronary Flow Velocity Reserve in Hypertensive Patients: Comparison with Calcium Channel Blocker

et al. 2007

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“…Using a 133 Xe infusion technique, Akopov et al also reported an increase of CBF in hypertensive patients after isradipine treatment, although they showed that treatment with isradipine reduced cerebral perfusion in almost half of the patients with internal carotid artery stenosis (7). Several other studies reported an increase of CBF in hypertensive patients after treatment with calcium channel blockers, as seen with transcranial Doppler (26)(27)(28).…”

Section: Discussionmentioning

confidence: 82%

Hemodynamic Influences of Azelnidipine, a Novel Calcium Channel Blocker, on Cerebral Circulation in Hypertensive Patients with Ischemic White Matter Lesions

et al. 2008

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“…L-type channel antagonists, such as dihydropyridines, phenylalkylamines, and benzothiazepines, are used for treatment of hypertension and angina pectoris (4,5,7,8,28,29). The dihydropyridine, phenylalkylamine, and benzothiazepine binding sites appear to encompass separate but partially overlapping regions located within domains III and IV (30 -32).…”

Section: Discussionmentioning

confidence: 99%

Roscovitine Binds to Novel L-channel (CaV1.2) Sites That Separately Affect Activation and Inactivation

Yarotskyy

Gao

et al. 2010

Journal of Biological Chemistry

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L-type (Ca V 1.2) calcium channel antagonists play an important role in the treatment of cardiovascular disease. (R)-Roscovitine, a trisubstituted purine, has been shown to inhibit L-currents by slowing activation and enhancing inactivation. This study utilized molecular and pharmacological approaches to determine whether these effects result from (R)-roscovitine binding to a single site. Using the S enantiomer, we find that (S)-roscovitine enhances inactivation without affecting activation, which suggests multiple sites. This was further supported in studies using chimeric channels comprised of N-and L-channel domains. Those chimeras containing L-channel domains I and IV showed (R)-roscovitine-induced slowed activation like that of wild type L-channels, whereas chimeric channels containing L-channel domain I responded to (R)-roscovitine with enhanced inactivation. We conclude that (R)-roscovitine binds to distinct sites on L-type channels to slow activation and enhance inactivation. These sites appear to be unique from other calcium channel antagonist sites that reside within domains III and IV and are thus novel sites that could be exploited for future drug development. Trisubstituted purines could become a new class of drugs for the treatment of diseases related to hyperfunction of L-type channels, such as Torsades de Pointes.Cardiac L-type (Ca V 1.2) channels are central to the regulation of a number of physiological processes (1, 2). Activation of these channels in cardiac and smooth muscle generates the calcium influx that triggers calcium release from the sarcoplasmic reticulum (3) to induce contraction. In contrast, inactivation of these channels provides a negative feedback mechanism to limit calcium influx into the cardiac myocyte, which helps protect from excessive calcium influx that can lead to cardiac arrhythmias (3). L-channel antagonists are routinely used to treat cardiovascular diseases, such as hypertension and angina pectoris (4 -8). Therefore, drugs that inhibit L-channel function have high clinical relevance.Roscovitine is a 2,6,9-trisubstituted purine that was originally developed as a selective blocker of cyclin-dependent kinases (9) and is currently undergoing phase II clinical trials as an anticancer drug (10). It has recently become apparent that roscovitine can affect voltage-dependent ion channels at clinically relevant concentrations (10 -50 M) (10 -13). We (14, 15) and others (16,17) have shown that (R)-roscovitine differentially affects voltage-dependent calcium channels. (R)-Roscovitine has two effects on Ca V 2 channels (N-type, P/Q-type, and R-type), which are a rapid onset agonist effect and a more slowly developing antagonist effect (14, 15). The agonist effect results from (R)-roscovitine specifically binding to activated Ca V 2 channels to slow channel closing (14, 15), which results in a significant enhancement of action potential induced calcium influx (14). The antagonist effect appears to result from (R)-roscovitine preferentially enhancing occupancy of a "resting" inac...

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Effects of Nicardipine on Coronary, Vertebral and Renal Arterial Flows in Patients with Essential Hypertension.

Cited by 11 publications

References 48 publications

Angiotensin Receptor Blocker Improves Coronary Flow Velocity Reserve in Hypertensive Patients: Comparison with Calcium Channel Blocker

Angiotensin Receptor Blocker Improves Coronary Flow Velocity Reserve in Hypertensive Patients: Comparison with Calcium Channel Blocker

Hemodynamic Influences of Azelnidipine, a Novel Calcium Channel Blocker, on Cerebral Circulation in Hypertensive Patients with Ischemic White Matter Lesions

Roscovitine Binds to Novel L-channel (CaV1.2) Sites That Separately Affect Activation and Inactivation

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