Importance of rostral ventrolateral medulla neurons in determining efferent sympathetic nerve activity and blood pressure.

Accentuated sympathetic nerve activity (SNA) is a risk factor for cardiovascular events. In this review, we investigate our working hypothesis that potentiated activity of neurons in the rostral ventrolateral medulla (RVLM) is the primary cause of experimental and essential hypertension. Over the past decade, we have examined how RVLM neurons regulate peripheral SNA, how the sympathetic and renin-angiotensin systems are correlated and how the sympathetic system can be suppressed to prevent cardiovascular events in patients.

Candesartan and insulin reduce renal sympathetic nerve activity in hypertensive type 1 diabetic rats.

The nonlinearity of cardiovascular regulation is higher in normal physiology, whereas several diseases are characterized by a reduction in this nonlinearity. Reduced nonlinearity of heart rate regulation is a robust risk factor for high mortality in patients with myocardial infarction. We investigated the changes in linear and nonlinear correlations of cardiovascular regulation after administering drugs in hypertensive diabetic rats.

Novel axonal projection from the caudal end of the ventrolateral medulla to the intermediolateral cell column.

We used an optical imaging technique to investigate whether axons of neurons in the caudal end of the ventrolateral medulla (CeVLM), as well as axons of neurons in the rostral ventrolateral medulla (RVLM), project to neurons in the intermediolateral cell column (IML) of the spinal cord. Brain stem-spinal cord preparations from neonatal normotensive Wistar-Kyoto and spontaneously hypertensive rats were stained with a voltage-sensitive dye, and responses to electrical stimulation of the IML at the Th2 level were detected as changes in fluorescence intensity with an optical imaging apparatus (MiCAM-01). The results were as follows: 1) depolarizing responses to IML stimulation during low-Ca high-Mg superfusion were detected on the ventral surface of the medulla at the level of the CeVLM, as well as at the level of the RVLM, 2) depolarizing responses were also detected on cross sections at the level of the CeVLM, and they had a latency of 24.

Electrophysiological properties of rostral ventrolateral medulla neurons in angiotensin II 1a receptor knockout mice.

We compared the electrophysiological properties of neurons in the rostral ventrolateral medulla of neonatal angiotensin II type 1a receptor knockout mice and wild-type mice with responses to angiotensin II, its type-1 receptor blocker candesartan, and its type-2 receptor blocker PD123319. Using the whole-cell patch-clamp technique, we examined the characteristics of rostral ventrolateral medulla neurons in brain stem-spinal cord preparations in which the sympathetic neuronal network is preserved. Baseline membrane potential and firing rate were almost similar between angiotensin II type 1a receptor knockout mice and wild-type mice.

Low-order chaos in sympathetic nerve activity and scaling of heartbeat intervals.

The mechanism of 1/f scaling of heartbeat intervals remains unknown. We recorded heartbeat intervals, sympathetic nerve activity, and blood pressure in conscious rats with normal or high blood pressure. Using nonlinear analyses, we demonstrate that the dynamics of this system of three variables is low-order chaos, and that sympathetic nerve activity leads to heartbeat interval and blood pressure changes.

[Comparison of ARB and ACEI for renoprotection in chronic glomerulonephritis].

This 1.5-year prospective study compared the effects of angiotensin II receptor blocker, candesartan(n = 21), and ACE inhibitor(ACEI, n = 23) on proteinuria and renal function in patients with moderate renal impairment due to chronic glomerulonephritis. Blood pressure reductions were comparable between both groups.

Potentiated sympathetic nervous and renin-angiotensin systems reduce nonlinear correlation between sympathetic activity and blood pressure in conscious spontaneously hypertensive rats.

Background: Patients with a reduced nonlinear component of heart rate regulation have a poorer outcome.

Methods And Results: We investigated whether a nonlinear correlation between renal sympathetic nerve activity (RSNA) and blood pressure or renal blood flow is reduced in conscious, spontaneously hypertensive rats (SHR) by comparing them with normotensive Wistar-Kyoto rats (WKY). We also determined the linearity and nonlinearity of the correlation in SHR who were given an angiotensin II receptor blocker, candesartan, orally for 2 weeks.