Biomedical subjects

Shun-Guang Wei

Publications and source records attributed to Shun-Guang Wei.

6 recordsLinked to original sources

PubMed2006

11beta-hydroxysteroid dehydrogenase type 2 activity in hypothalamic paraventricular nucleus modulates sympathetic excitation.

Aldosterone stimulates the sympathetic nervous system by binding to a select population of brain mineralocorticoid receptors (MR). These MR have an equal affinity for corticosterone that is present in substantially higher concentrations, but are held in reserve for aldosterone by activity of the enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD-2), which converts corticosterone to an inactive metabolite. Thus, colocalization of MR and 11beta-HSD-2 activity may help identify brain regions that mediate the effects of aldosterone. The present studies tested the hypothesis that 11beta-HSD-2 activity regulates MR-mediated responses in the paraventricular nucleus (PVN) of the hypothalamus, a forebrain region implicated in sympathetic regulation. Real-time-polymerase chain reaction revealed the presence of 11beta-HSD-2 mRNA in PVN. In anesthetized adult male Sprague-Dawley rats, microinjection of the 11beta-HSD-2 inhibitor carbenoxolone (CBX) into PVN increased mean arterial pressure, heart rate, and renal sympathetic nerve activity. Intracerebroventricular injections of CBX excited PVN neurons and increased mean arterial pressure, heart rate, and renal sympathetic nerve activity. The ability of CBX to increase sympathetic activity by inhibiting 11beta-HSD-2, thereby permitting corticosterone to activate MR, was confirmed by the following: Intracerebroventricular glycyrrhizic acid, another 11beta-HSD-2 inhibitor, mimicked the sympathoexcitatory effects of CBX; the sympathoexcitatory effects of CBX were blocked by spironolactone, a MR antagonist. Neither CBX nor glycyrrhizic acid elicited a response in adrenalectomized rats. These findings suggest that MR in PVN contribute to sympathetic regulation and may be activated by aldosterone or corticosterone (or cortisol in humans) depending on the state of 11beta-HSD-2 activity.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗

PubMed2004

Brain angiotensin-converting enzyme activity and autonomic regulation in heart failure.

Several recent studies suggest an important role for the brain renin-angiotensin system in the pathogenesis of heart failure. Angiotensin-converting enzyme (ACE) activity and binding of angiotensin type 1 (AT1) receptors, which mediate the central effects of ANG II, are increased in heart failure. The present study examined the relationship between brain ACE activity and the autonomic dysregulation characteristic of rats with congestive heart failure. Rats with heart failure (HF) induced by coronary artery ligation and sham-operated control (SHAM) rats were treated with chronic (28 days) third cerebral ventricle [intracerebroventricular (ICV)] or intraperitoneal (IP) infusion of a low dose of the ACE inhibitor enalaprilat (ENL) or vehicle (VEH). VEH-treated HF rats had increased sodium consumption, reduced urine sodium and urine volume, and increased sympathetic nerve activity with impaired baroreflex regulation. These responses were minimized or prevented by ICV ENL started 24 h after coronary ligation. IP ENL at the low dose used in these studies had no beneficial effects on HF rats. Neither IP nor ICV ENL had any substantial effect on the SHAM rats. The findings confirm a critically important contribution of the brain renin-angiotensin system to the pathophysiology of congestive heart failure.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2003

Heart failure and the brain: new perspectives.

Despite recent therapeutic advances, the prognosis for patients with heart failure remains dismal. Unchecked neurohumoral excitation is a critical element in the progressive clinical deterioration associated with the heart failure syndrome, and its peripheral manifestations have become the principal targets for intervention. The link between peripheral systems activated in heart failure and the central nervous system as a source of neurohumoral drive has therefore come under close scrutiny. In this context, the forebrain and particularly the paraventricular nucleus of the hypothalamus have emerged as sites that sense humoral signals generated peripherally in response to the stresses of heart failure and contribute to the altered volume regulation and augmented sympathetic drive that characterize the heart failure syndrome. This brief review summarizes recent studies from our laboratory supporting the concept that the forebrain plays a critical role in the pathogenesis of ischemia-induced heart failure and suggesting that the forebrain contribution must be considered in designing therapeutic strategies. Forebrain signaling by neuroactive products of the renin-angiotensin system and the immune system are emphasized.

Animals↗

PubMed2003

Cardiovascular and renal sympathetic activation by blood-borne TNF-alpha in rat: the role of central prostaglandins.

In pathophysiological conditions, increased blood-borne TNF-alpha induces a broad range of biological effects, including activation of the hypothalamic-pituitary-adrenal axis and sympathetic drive. In urethane-anesthetized adult Sprague-Dawley rats, we examined the mechanisms by which blood-borne TNF-alpha activates neurons in paraventricular nucleus (PVN) of hypothalamus and rostral ventrolateral medulla (RVLM), two critical brain regions regulating sympathetic drive in normal and pathophysiological conditions. TNF-alpha (0.5 microg/kg), administered intravenously or into ipsilateral carotid artery (ICA), activated PVN and RLVM neurons and increased sympathetic nerve activity, arterial pressure, and heart rate. Responses to intravenous TNF-alpha were not affected by vagotomy but were reduced by mid-collicular decerebration. Responses to ICA TNF-alpha were substantially reduced by injection of the cyclooxygenase inhibitor ketorolac (150 microg) into lateral ventricle. Injection of PGE(2) (50 ng) into lateral ventricle or directly into PVN increased PVN or RVLM activity, respectively, and sympathetic drive, with shorter onset latency than blood-borne TNF-alpha. These findings suggest that blood-borne cytokines stimulate cardiovascular and renal sympathetic responses via a prostaglandin-dependent mechanism operating at the hypothalamic level.

Animals↗

PubMed2002

Forebrain-mediated adaptations to myocardial infarction in the rat.

Recent studies suggest that the forebrain contributes to the circulatory derangements leading to heart failure after myocardial injury. We tested that hypothesis by examining the effect of myocardial infarction (MI) or sham MI (MI-s) on neurohumoral regulation in rats with prior anteroventral (AV) third ventricle lesion (AV3V-x) or sham lesion (AV3V-s). AV3V-s/MI rats had higher sodium intake, lower urine volume, and lower urinary sodium excretion than AV3V-s/MI-s rats. AV3V-x/MI rats had lower sodium intake and higher urine volume than AV3V-s/MI or AV3V-s/MI-s rats and urinary sodium excretion comparable to AV3V-s/MI-s rats. AV3V-x had no effect on baseline plasma renin activity (PRA). One week after MI, PRA had increased in AV3V-s but decreased in AV3V-x rats. AV3V-x reduced renal sympathetic nerve activity in MI and MI-s rats. AV3V-x improved baroreflex function in MI rats but diminished it in MI-s rats. Survival beyond 2 wk was lower in the AV3V-x/MI rats than in all other groups. These results confirm a critical role for the forebrain in the neurohumoral adjustments to MI.

Adaptation, Physiological↗

PubMed2002

Forebrain renin-angiotensin system has a tonic excitatory influence on renal sympathetic nerve activity.

All elements of the renin-angiotensin system (RAS) are present in the forebrain, particularly in circumventricular organs surrounding the third cerebral ventricle. We tested the hypothesis that forebrain angiotensin-converting enzyme (ACE) has a tonic excitatory influence on sympathetic drive. Neurally intact and sinoaortic-denervated pentobarbital-anesthetized rats were treated with forebrain-directed intracarotid artery (ICA) versus intravenous injections of angiotensin I (ANG I) and of the ACE inhibitor captopril. In intact rats, ICA ANG I elicited a rise in arterial pressure and a concomitant reduction in renal sympathetic nerve activity (RSNA; ICA captopril elicited the opposite responses). In barodenervated rats, ICA ANG I increased and ICA captopril decreased arterial pressure and RSNA in parallel; intravenous ANG I had no effect on RSNA. The findings suggest that the intrinsic forebrain RAS has a tonic excitatory influence on sympathetic drive that is overshadowed in normal rats by baroreflex mechanisms, but may assume a more prominent role in pathophysiological states (e.g., heart failure) in which baroreflex mechanisms are impaired and RAS activity is augmented.

Angiotensin I↗