Efficacy of clonidine in patients with essential hypertension with neurovascular contact of the rostral ventrolateral medulla.

The rostral ventrolateral medulla (RVLM) is an important center for regulation of sympathetic nerve activity. Several clinical studies have suggested an association between neurovascular contact (NVC) of RVLM and essential hypertension. Microvascular decompression (MVD) of RVLM decreases blood pressure (BP) in hypertensive patients with NVC of this region. Therefore, MVD could be a useful therapeutic strategy to reduce BP in these patients. However, as MVD is an invasive procedure, it is worthy to seek useful antihypertensive agents for hypertensive patients with NVC. It is reported that sympathetic nerve activity is elevated in patients with hypertension accompanied by NVC of RVLM. It is anticipated that sympatholytic agents could be effective in lowering BP in these patients. In this study, we investigated the efficacy of clonidine, an alpha2 adrenergic agonist, in essential hypertensives with NVC of RVLM. Thirty consecutive essential hypertensive patients with NVC and 30 consecutive essential hypertensive patients without contact were treated with clonidine for 4 weeks, and decreases in BP and plasma norepinephrine levels were compared between the two groups. Decreases in BP and plasma norepinephrine levels were significantly greater in patients with NVC than in those without contact. These results suggest that clonidine exhibits significantly greater reductions of BP and sympathetic nerve activity in essential hypertensive patients with NVC compared with those without contact of the rostral ventrolateral medulla.

Efficacy of an L- and N-type calcium channel blocker in hypertensive patients with neurovascular compression of the rostral ventrolateral medulla.

The rostral ventrolateral medulla is an important regulation center of sympathetic nerve activity. Several clinical studies have indicated a possible association between essential hypertension and neurovascular compression of the rostral ventrolateral medulla. We have found that patients with essential hypertension and neurovascular compression of the rostral ventrolateral medulla by adjacent arteries have increased sympathetic nerve activity and that microvascular decompression of the rostral ventrolateral medulla normalizes blood pressure and sympathetic nerve activity. Although sympatholytic agents are expected to lower blood pressure in these patients, this remains to be clarified. In this study, we evaluated the effect of cilnidipine, a calcium channel blocker that blocks both vascular L-type and sympathetic N-type Ca(2+) channels in hypertensive patients with neurovascular compression. Using high-resolution magnetic resonance imaging, 46 patients with untreated essential hypertension were distributed into those with and without neurovascular compression of the rostral ventrolateral medulla. All patients were prescribed 10 mg of cilnidipine for 16 weeks. Office and home blood pressure, plasma norepinephrine and left ventricular mass index were measured by echocardiography before and after cilnidipine treatment, and changes were compared between the two groups. At baseline, plasma norepinephrine was significantly higher in patients with neurovascular compression. Decreases in office and home blood pressure, plasma norepinephrine and left ventricular mass index were significantly greater in patients with neurovascular compression. These results suggest that cilnidipine lowers blood pressure by inhibiting enhanced sympathetic nerve activity and reduces left ventricular mass in hypertensive patients with neurovascular compression of the rostral ventrolateral medulla.

Prognostic significance of ankle-brachial index, brachial-ankle pulse wave velocity, flow-mediated dilation, and nitroglycerin-mediated dilation in end-stage renal disease.

BACKGROUND: Identifying patients at high risk of cardiovascular disease is important in managing patients undergoing hemodialysis. METHODS: We evaluated a series of prognostic values: flow-mediated dilation (FMD) and nitrogen-mediated dilation (NMD), an index of endothelium-dependent and endothelium-independent function, respectively, ankle-brachial index (ABI), and brachial-ankle pulse wave velocity (baPWV) in patients undergoing chronic hemodialysis. RESULTS: A cohort of 199 patients was studied. At entry, these values were examined and the prognostic significances were investigated. In estimating the significance of baPWV, patients with ABI <0.9 were excluded. During the follow-up period, 24 deaths occurred including 14 cardiovascular and 10 noncardiovascular fatal events. Overall, the survival rates were significantly lower in the low ABI than in the high ABI group, but the survival rates were not significantly different between the high and low FMD, NMD, or baPWV groups. Cardiovascular survival rates were significantly lower in the low ABI than in the high ABI group, and in the high baPWV than in the low baPWV group. The survival rates were not significantly different between the high and low FMD or NMD groups. CONCLUSIONS: Screening hemodialysis patients by means of ABI and baPWV but not FMD or NMD provides complementary information in identifying a high-risk population in these patients.

New index of regional arterial stiffness assessed by tissue Doppler imaging.

BACKGROUND: Although brachial-ankle pulse wave velocity is a widely used index of arterial stiffness, there are several limitations of this method. The actual length of an artery used for measuring pulse wave velocity is estimated based on an anatomical correction value, and brachial-ankle pulse wave velocity is directly affected by systemic blood pressure or vascular occlusion. Thus, the aim of this study was to determine whether aortic wall strain rate as measured by tissue Doppler imaging is a more useful modality for evaluating regional arterial stiffness than brachial-ankle pulse wave velocity. METHODS: Seventy-two patients (18 to 78 years) with normal cardiac function and without large vessel complications were enrolled in this study. RESULTS: A significant positive correlation was found between brachial-ankle pulse wave velocity and age, and brachial-ankle pulse wave velocity increased with age (r = 0.64, P < 0.0001).A significant negative correlation was found between strain rate and age, and strain rate decreased with age (r = -0.44, P < 0.05). A significant correlation was also found between brachial-ankle pulse wave velocity and systolic blood pressure (r = 0.45, P < 0.02), but not between strain rate and systolic blood pressure.There was no significant difference in brachial-ankle pulse wave velocity between hyperlipidaemic and normolipidaemic subjects. However, strain rate was lower in hyperlipidaemic than in normolipidaemic subjects (P < 0.05). CONCLUSION: Strain rate on the ascending aortic wall is a novel and more accurate index of regional arterial stiffness than brachial-ankle pulse wave velocity.

Beneficial effects of combination therapy with angiotensin II receptor blocker and angiotensin-converting enzyme inhibitor on vascular endothelial function.

The combination of angiotensin I-converting enzyme inhibitors and angiotensin receptor blockers has been shown to be more effective than the individual drugs alone in the treatment of chronic kidney disease and chronic heart failure. In the present study, we evaluated the effect of treatment with the calcium channel blocker amlodipine or the angiotensin I-converting enzyme inhibitor perindopril on vascular endothelial function and arteriosclerosis in patients with essential hypertension who had already been receiving angiotensin receptor blocker monotherapy. Thirty-two patients with essential hypertension treated with angiotensin receptor blocker monotherapy were randomized to receive 5 mg of amlodipine (n=16) or 4 mg of perindopril (n=16) once daily in the morning for 24 weeks. The patients were evaluated before and after therapy to assess changes in blood pressure, flow-mediated vasodilation (a parameter of vascular endothelial function), and brachial-ankle pulse wave velocity (a parameter of arteriosclerosis). Before treatment, there were no significant differences in the above parameters between groups. After treatment, there was a similar significant decrease in blood pressure in both groups. Flow-mediated vasodilation increased significantly in the perindopril group compared with the amlodipine group; however, the decrease in brachial-ankle pulse wave velocity was not significantly different between groups. In conclusion, these results suggest that the angiotensin I-converting enzyme inhibitor perindopril is superior to the calcium channel blocker amlodipine for reducing vascular endothelial dysfunction when co-administered with angiotensin receptor blockers in patients with essential hypertension.