Effects of a New Calcium Channel Blocker, Azelnidipine, on Systemic Hemodynamics and Renal Sympathetic Nerve Activity in Spontaneously Hypertensive Rats

Abstract

Antihypertensive treatment with dihydropyridine calcium channel blockers elicits sympathetic nerve activation, which may contribute to cardiovascular events. However, recent clinical studies showed that treatment with azelnidipine, a new dihydropyridine calcium channel blocker, significantly reduced blood pressure in hypertensive patients while either maintaining or actually decreasing heart rate (HR). In this study, we exam- 1023)Key Words: azelnidipine, amlodipine, renal sympathetic nerve activity (RSNA), spontaneously hypertensive rats (SHR), heart rate (HR)

Effects of Antihypertensive Drugs and Exercise Training on Insulin Sensitivity in Spontaneously Hypertensive Rats

“…In the present study, the azelnidipine-improved IS was associated with a significant reduction of SBP-LFamp. Although azelnidipine does not have an N-type calcium channel blocking action, it has a unique long-acting dihydropyridine-based calcium antagonistic action with sympathoinhibitory effects (29,30). Taken together, these results suggest that the sympathoinhibitory action is necessary for CCBs to exert a beneficial effect on IS.…”

Azelnidipine attenuates glomerular damage in Dahl salt-sensitive rats by suppressing sympathetic nerve activity

“…Next, a catheter was inserted into the left external jugular vein for infusion of amlodipine (0.5 mg kg À1 , bolus injection; n¼5, Sigma-Aldrich Japan, Tokyo, Japan) or azelnidipine (0.1 mg kg À1 , bolus injection; n¼5, provided by Daiichi Sankyo, Tokyo, Japan). The dosage of amlodipine and azelnidipine was decided in reference to the procedure of Shokoji et al 15 A dorsal incision was then made under sterile conditions, and the left kidney was exteriorized. Glomerular microcirculation was recorded for 30 min after infusion by a charge-coupled device videomicroscope placed in direct contact with the exposed surface of the kidney, as described previously.…”

Combination Therapy with Renin-Angiotensin System Inhibitors and the Calcium Channel Blocker Azelnidipine Decreases Plasma Inflammatory Markers and Urinary Oxidative Stress Markers in Patients with Diabetic Nephropathy

“…It has been suggested that CCBs may activate the SNS and increase heart rates because of their potent hypotensive action (42,43). Unlike other dihydropyridine-type CCBs, AZ has a unique action of inhibiting SNS, and it indeed decreases, rather than increases, the heart rate after oral administration (6,44). Antihypertensive treatment with AZ attenuates reflex-induced sympathetic activation and enhances endothelial nitric oxide synthase expression levels in the brain as well as in the heart and aorta (45).…”