The incidence of cerebrovascular diseases increases significantly with aging. This study aimed to test the hypothesis that aging may influence the protein kinase A (PKA)-dependent vasodilation via RyR/BKCa pathway in the middle cerebral arteries (MCA). Male Sprague-Dawley rats were randomly divided into control (4-6 month-old) and aged (24-month-old) groups. The functions of MCA and ion channel activities in smooth muscle cells were examined using myograph system and patch-clamp. Aging decreased the isoproterenol/forskolin-induced relaxation in the MCA. Large-conductance Ca(2+)-activated-K(+) (BKCa) channel inhibitor, iberiotoxin, significantly attenuated the forskolin-induced vasodilatation and hyperpolarization in the young group, but not in the aged group. The amplitude and frequency of spontaneous transient outward currents (STOCs) were significantly decreased in the aged group. Single channel recording revealed that the mean open time of BKCa channels were decreased, while an increased mean closed time of BKCa channels were found in the aged group. The Ca(2+)/voltage sensitivity of the channels was decreased accompanied by reduced BKCa alpha and beta1-subunit, the expression of RyR2, PKA-Calpha and PKA-Cbeta subunits were also declined in the aged group. Aging induced down-regulation of PKA/BKCa pathway in cerebral artery in rats. The results provides new information on further understanding in cerebrovascular diseases resulted from age-related cerebral vascular dysfunction.

• MeSH
• arteriae cerebrales * fyziologie   MeSH
• down regulace MeSH
• kolforsin MeSH
• krysa rodu rattus MeSH
• potkani Sprague-Dawley MeSH
• proteinkinasy závislé na cyklickém AMP * MeSH
• stárnutí MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Prenatal exposure to caffeine can cause developmental problems. This study determined chronic influence of prenatal caffeine at relatively higher doses on cognitive functions in the rat offspring. Pregnant Sprague-Dawley rats (4-month-old) were exposed to caffeine (20 mg/kg, twice a day) for whole pregnancy from gestational day 4. Fetal and offspring body and brain weight was measured. Learning and memory were tested in adult offspring with Morris water maze. Learning and memory-related receptors were measured. The exposure to prenatal caffeine not only caused fetal growth restriction, but also showed long-term effects on learning and memory in the offspring. The caffeine offspring exhibited longer escape latency and path length in navigation testing. The number of passing the target was significantly reduced in those offspring. The expression of adenosine A(1) and A(2A) receptors, nuclear PKA C(alpha), C(beta) subunits, and pCREB were significantly increased in the fetal and neonatal brain, and suppressed in the hippocampus of the adult offspring. The expression of BDNF and TrkB were reduced regardless of various ages. The results suggest that intrauterine programming dysfunction of adenosine receptors and the down-stream of cAMP/PKA/pCREB system may play an important role in prenatal caffeine induced cognition disorders in the adult offspring.

• MeSH
• bludiště - učení účinky léků   fyziologie   MeSH
• kofein toxicita   MeSH
• krysa rodu rattus MeSH
• mozkový neurotrofický faktor metabolismus   MeSH
• paměť účinky léků   fyziologie   MeSH
• poruchy paměti chemicky indukované   diagnóza   metabolismus   MeSH
• potkani Sprague-Dawley MeSH
• protein vázající element responzivní pro cyklický AMP metabolismus   MeSH
• proteinkinasy závislé na cyklickém AMP metabolismus   MeSH
• purinergní receptory P1 metabolismus   MeSH
• signální transdukce účinky léků   fyziologie   MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice chemicky indukované   diagnóza   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH