Aging Reduces L-Type Calcium Channel Current and the Vasodilatory Response of Small Mesenteric Arteries to Calcium Channel Blockers
| Autor: | Al-Manar Al-Busaidi, Fathi Mansour, Musbah O Tanira, Isehaq Al-Husseini, Sulayma Albarwani, Sultan Al-Siyabi, Abdul Aleem Khan, Abdulla Al-Kaabi, Safa Al-Hadhrami, Intisar Al-Lawati |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Physiology Vasodilation 030204 cardiovascular system & hematology lcsh:Physiology 03 medical and health sciences 0302 clinical medicine Nifedipine Internal medicine Physiology (medical) medicine L-type calcium channel Diltiazem Mesenteric arteries mesenteric arteries Original Research calcium channel blockers lcsh:QP1-981 business.industry Calcium channel aging F344 rats 030104 developmental biology Endocrinology medicine.anatomical_structure Verapamil business voltage-gated calcium channel voltage gated calcium channels medicine.drug Myograph |
| Zdroj: | Frontiers in Physiology Frontiers in Physiology, Vol 7 (2016) |
| ISSN: | 1664-042X |
| Popis: | Calcium channel blockers are widely used to treat cardiovascular disease (CVD) including hypertension. As aging is an independent risk factor for CVD, the use of calcium channel blockers increases with increasing age. Hence, this study was designed to evaluate the effect of aging on the sensitivity of small mesenteric arteries to L-type voltage-gated calcium channel (LTCC) blockers and also to investigate whether there was a concomitant change in calcium current density. Third order mesenteric arteries from male F344 rats, aged 2.5 - 3 months (young) and 22 - 26 months (old) were mounted on wire myograph to measure the tension during isometric contraction. Arteries were contracted with 100 mM KCl and were then relaxed in a cumulative concentration-response dependent manner with nifedipine (0.1nM - 10 µM), verapamil (0.1nM-10 µM) or diltiazem (0.1nM - 10µM). Relaxation-concentration response curves produced by cumulative concentrations of three different calcium channel blockers (CCBs) in arteries of old rats were shifted to the right with statistically significant IC50s. pEC50 ± s.e.m: (8.37 ± 0.06 vs 8.04 ± 0.05 , 7.40 ± 0.07 vs 6.81 ± 0.04 and 6.58 ± 0.07 vs 6.34 ± 0.06) in young vs old. It was observed that the maximal contractions induced by 100 mM KCl, phenylephrine and reversed by sodium nitroprusside were not different between young and old groups. However, Bay K 8644 increased resting tension by 23±4.8% in young arteries and 4.7±1.6% in old arteries. LTCC current density were also significantly lower in old arteries (-2.77 ± 0.45 pA/pF) compared to young arteries (-4.5 ± 0.40 pA/pF); with similar steady-state activation and inactivation curves. Parallel to this reduction, the expression of Cav1.2 protein was reduced by 57 ± 5% in arteries from old rats compared to those from young rats. In conclusion, our results suggest that aging reduces the response of small mesenteric arteries to the vasodilatory effect of the CCBs and this may be due to, at least in part, reduced current density of LTCC. |
| Databáze: | OpenAIRE |
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