The Beta-1-Receptor Blocker Nebivolol Elicits Dilation of Cerebral Arteries by Reducing Smooth Muscle [Ca2+]i

K

Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Induces Relaxations of Peripheral and Cerebral Arteries, which are Differentially Impaired by Aging

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a well-known neuropeptide, which also has vasomotor effects. However, little is known regarding its age-related and organ-specific vasomotor effects. We hypothesized that the vasomotor effects of PACAP depend on the tissue origin of the vessels and aging substantially modulates its actions. Thus, carotid (CA) and basilar arteries (BA) were isolated from young (2 months old), middle age (12 months old), and old (30 months old) rats. Their vasomotor responses were measured with an isometric myograph (DMT610M) in response to cumulative concentrations of PACAP1-38 (10-9-10-6 M). PACAP1-38 induced (1) significantly greater concentration-dependent relaxations in CA compared to that of BA of young, middle age, and old rats; (2) relaxations of CA significantly decreased, whereas they did not change substantially in BA, as a function of age; (3) sodium nitroprusside (SNP)-induced relaxation did not change after PACAP1-38 administration in any conditions; and (4) inhibition of PAC1 receptors by selective PAC1 receptor blocker (PACAP6-38) completely diminished the responses to PACAP in all age groups of BA and CA. In conclusion, these findings suggest that PACAP1-38 has greater vasomotor effect in CA than that in BA, whereas aging has less effect on PACAP-induced relaxation of cerebral arteries and BA than that in peripheral arteries and CA suggesting that the relaxation to PACAP is maintained in cerebral arteries even in old age

Hemolyzed Blood Elicits a Calcium Antagonist and High CO2 Reversible Constriction via Elevation of [Ca2+] in Isolated Cerebral Arteries

LBL

Vénás mikroerek vazomotor funkciója hiperhomociszteinémiában = Vasomotor function of venous microvessels in hyperhomocysteinemia

Kutatásaink kiderítették a konstriktor prosztaglandinok döntő szerepét mind a vénás erek mind az agyi erek vasomotor működésében, egészséges és kóros körülmények között. Ez idáig úgy gondolták, hogy a konstriktor prosztaglandinoknak csak kóros szerepe van. A homocystein magas szintje csökkenti a vaszkuláris működést és thrombotikus irányban tereli az endothelium működését, ami felelős lehet a vénás thromboembolitikus elváltozások kialakulásában. Ugyanakkor kimutattuk, hogy a konstriktor prosztaglandinoknak fontos szerepe van az agyi autóreguláció kialakulásában. Feltehető, hogy ezen eredmények elméleti alapot szolgáltatnak új gyógyszertermékek kidolgozásához. | These investigations revealed the important role of constrictor prostaglandins, not only in diseased conditions, but in normal conditions, as well. These results draw the attention again the utmost importance of constrictor prostaglandins in the maintenance of normal and diseased vascular functions, especially to their role in antithrombotic events. In addition, we have shown that constrictor prostaglandins are importantly involved in the modulation of and autoregulation of cerebral circulation, which have not been known previously. These new pathways provide the theoretical basis for the development of new drugs