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

Takao Sakuma, Satoshi Morimoto, Yasuko Aota, Nobuyuki Takahashi, Nagaoki Toyoda, Atsushi Kosaki, Minoru Maehara, Noboru Tanigawa, Koshi Ikeda, Satoshi Sawada and Toshiji Iwasaka

Abstract
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 α2 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.

In the MS patients after clonidine, the haemodynamic responses varied. In five out of ten MS patients, as in the controls, there was a fall in blood pressure and superior mesenteric vascular resistance, while finger temperature rose. There was no haemodynamic response to clonidine in the other five MS patients. In eight out of ten MS patients there was no rise in plasma growth hormone levels after clonidine. The abnormal haemodynamic responses to clonidine, taken in conjunction with the previous physiological studies, suggest involvement of central sympathetic interconnections in five of the MS patients, probably as part of the demyelinating process.

Anonymoose wrote:This sounds eerily like the random CCSVI angioplasty results. Works in some...doesn't in others.

The warm finger effect was kind of exciting.

http://onlinelibrary.wiley.com/doi/10.1 ... x/abstract

In the MS patients after clonidine, the haemodynamic responses varied. In five out of ten MS patients, as in the controls, there was a fall in blood pressure and superior mesenteric vascular resistance, while finger temperature rose. There was no haemodynamic response to clonidine in the other five MS patients. In eight out of ten MS patients there was no rise in plasma growth hormone levels after clonidine. The abnormal haemodynamic responses to clonidine, taken in conjunction with the previous physiological studies, suggest involvement of central sympathetic interconnections in five of the MS patients, probably as part of the demyelinating process.

Clonidine treats high blood pressure by stimulating α2 receptors in the brain, which decreases cardiac output and peripheral vascular resistance, lowering blood pressure. It has specificity towards the presynaptic α2 receptors in the vasomotor center in the brainstem. This binding decreases presynaptic calcium levels, and inhibits the release of norepinephrine (NE). The net effect is a decrease in sympathetic tone.[20]
It has also been proposed that the antihypertensive effect of clonidine is due to agonism on the I1-receptor (imidazoline receptor), which mediates the sympatho-inhibitory actions of imidazolines to lower blood pressure

Clonidine improves cognitive deficits by regulating synaptic strength in chronic cerebral hypoperfused rats
Uncategorized11/08/2012 17:12:460 Comments
Changjun Li, Yun Lu, Qing Lv, Xulin Xu, Lianjun Guo

Department of Pharmacology, School of Basic Medical Sciences, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China

Corresponding author: Lianjun Guo, gljyl@yahoo.com.cn.

Abstract
Permanent bilateral occlusion of the common carotid arteries in rats is an established experimental model to investigate chronic cerebral hypoperfusion on cognitive function and neurodegenerative processes. Three weeks after surgery, intraperitoneal injection of clonidine (0.05 mg/kg) was administered once a day. After 1 week of treatment, the Morris water maze was utilized to evaluate the effect of clonidine on spatial learning and memory performance. Electrophysiological recordings were performed in vivo. A concentric bipolar stimulating electrode was placed in the ipsilateral Schaffer collaterals of the right hemisphere. Recording electrode was positioned in the CA1 stratum radiatum. LTP was induced with four trains of 100 Hz, 1s stimulation separated by 5 minutes. Immunofluorescence staining was used to investigate the influence of clonidine on pyramidal neuron numbers and expression of HCN1 and HCN2 in hippocampus CA1. Latency to find the platform of chronic hypoperfusion treated rats was longer than sham-operated group (P < 0.01). Escape latency of clonidine group was significantly shorter compared with the ischemic group (P < 0.05). Induction of LTP in hippocampal CA1 region was significantly enhanced in ischemic group compared with sham-operated rats (P < 0.01) and this pathological enhancement was attenuated by clonidine (P < 0.05). In hippocampal CA1 subdivisions, pyramidal neuron numbers were significantly lower in the ischemic group, which could be reduced by Clonidine. In the ischemic group, the fluorescence intensity of HCN1 and HCN2 was significantly lower than sham-operated group, and clonidine could improve the expression of HCN1 and HCN2 in CA1 region of ischemic rats. Thus, clonidine improves cognitive deficit possibly by inhibiting decreased expression of HCN1 and HCN2 channels to alleviate the over-excited synapse, caused by chronic cerebral ischemia.

Thus, clonidine improves cognitive deficit possibly by inhibiting decreased expression of HCN1 and HCN2 channels to alleviate the over-excited synapse, caused by chronic cerebral ischemia.

In hippocampal CA1 subdivisions, pyramidal neuron numbers were significantly lower in the ischemic group, which could be reduced by Clonidine.

MarkW wrote:Hello Anonymoose and anyone considering Clonidine,
Please do not use Clonidine as an angioplasty alternative. Get the venoplasty done by a leading practitioner (diagnosis with CV +IVUS) before considering Clonidine and then under medical supervision. I was an industrial pharmacist and my industry loves long term use of medicine. But CCSVI syndrome produces a physical problem (stenoses) and needs a physical treatment first.
Kind regards,
MarkW

Music wrote:Anonymoose,
I am very happy for you that clonidine is doing great things for you. Unfortunately it was not so for me. In the middle of my two year stint with baclofen in the late ‘90’s, my neuro had me take clonidine as well. WHOA! Mentally and emotionally I felt like I was going to fall off the edge of the earth. Only took it for a month. Quit the baclofen also as I had gotten EXTREME insomnia from it. Was it the mixing of the two, I don’t know. Neuro said one thing, head nurse said another. As all of us will react differently to different treatments, I guess I’m not a good candidate for meds. I am glad you are having good luck.

P.S. LDN didn’t help me also. Haven’t been on anything since.

Anonymoose wrote:I'm pretty sure I don't have CCSVI. I don't have any of the trademark symptoms and I've had a lifetime of high stress levels to botch my hpa-axis w/o any other contributing factors.

Cece wrote:This is really interesting too. Awhile back, I speculated that we might be self-selecting: that those of us who went in to get checked for CCSVI were more likely to have CCSVI because we recognized the symptoms and we had them. So you have self-selected yourself not to get checked because you do not recognize the symptoms in yourself.

If CCSVI is present in nearly 100% of pwMS, then we all are almost guaranteed to have CCSVI and self-selecting isn't a big issue.
Otherwise self-selecting could explain why the very high percentages of CCSVI in MS that are being seen clinically are not being seen in the ultrasound studies.

I also remember a conversation with a fellow patient back in 2011, right before she had angioplasty done, and afterwards she said that she was having improvements in a lot of the usual symptoms that she hadn't even been aware that she had until they improved.

(And I hope you are right about those of us who've had big improvements no longer needing to worry. I still worry.)