Arterioles in cerebral amyloid angiopathy and vascular dementia

Background Small cerebrovascular lesions are one of the most important factors in cerebral amyloid angiopathy （CAA） and vascular dementia （VaD）. We analyzed the difference of arteriolar pathology between CAA patients （CAAs） and vascular dementia patients without CAA （VaDs）. Methods Ten deceased CAAs and twelve deceased VaDs were available for this study. Five deceased patients without known cerebrovascular diseases served as controls. These patients were all autopsy cases. All transversely cut arterioles in the gray matter and white matter with an external diameter equal to or larger than 30 um and with a maximum of 300 um were examined. The internal and external diameters of arterioles were measured. Results The external diameter of gray matter arterioles in the CAAs was significantly greater than in controls. In gray matter arterioles, the diameter of the lumen in VaDs was markedly smaller than in the CAAs, whereas there was no significant difference between CAAs and controls. CAAs and VaDs may cause remarkable thickening of the arteriolar walls in either white matter or gray matter. The sclerotic index of arterioles in VaDs was significantly greater than in CAAs and controls. Conclusions Stenosis of arterioles occurred in both CAA and VaD, but the tendency was greater in VaD. Arterioles of CAA were also expanded in gray matter, which may be related to lobar hemorrhage. The loss and/or degeneration of vascular smooth muscle cells was predominant in CAA, while the over-proliferation of vascular smooth muscle cells was areater in VaD.     

5-HT7 receptors mediate dilation of rat cremaster muscle arterioles in vivo

Objective

Serotonin (5-HT) infusion in vivo causes hypotension and a fall in total peripheral resistance. However, the vascular segment and the receptors that mediate this response remain in question. We hypothesized that 5-HT₇ receptors mediate arteriolar dilation to 5-HT in skeletal muscle microcirculation.

Methods

Cremaster muscles of isoflurane-anesthetized male Sprague-Dawley rats were prepared for in vivo microscopy of third- and fourth-order arterioles and superfused with physiological salt solution at 34°C. Quantitative real-time PCR (RT-PCR) was applied to pooled samples of first- to third-order cremaster arterioles (2–4 rats/sample) to evaluate 5-HT₇ receptor expression.

Results

Topical 5-HT (1–10 nmols) or the 5-HT_1/7 receptor agonist, 5-carboxamidotryptamine (10–30 nM), dilated third- and fourth-order arterioles, responses that were abolished by 1 μM SB269970, a selective 5-HT₇ receptor antagonist. In contrast, dilation induced by the muscarinic agonist, methacholine (100 nmols) was not inhibited by SB269970. Serotonin (10 nmols) failed to dilate cremaster arterioles in 5-HT₇ receptor knockout rats whereas arterioles in wild-type litter mates dilated to 1 nmol 5-HT, a response blocked by 1 μM SB269970. Quantitative RT-PCR revealed that cremaster arterioles expressed mRNA for 5-HT₇ receptors.

Conclusions

5-HT₇ receptors mediate dilation of small arterioles in skeletal muscle and likely contribute to 5-HT-induced hypotension, in vivo.