TY - JOUR
T1 - Aging reduces L-type calcium channel current and the vasodilatory response of small mesenteric arteries to calcium channel blockers
AU - Albarwani, Sulayma A.
AU - Mansour, Fathi
AU - Khan, Abdul Aleem
AU - Al-Lawati, Intisar
AU - Al-Kaabi, Abdulla
AU - Al-Busaidi, Al Manar
AU - Al-Hadhrami, Safa
AU - Al-Huseini, Isehaq
AU - Al-Siyabi, Sultan
AU - Tanira, Musbah O.
N1 - Funding Information:
This work was funded by The National Research Council grant # RC/SQU/MED/PHYS/12/01 to SA.
Publisher Copyright:
© 2016 Albarwani, Mansour, Khan, Al-Lawati, Al-Kaabi, Al-Busaidi, Al-Hadhrami, Al-Husseini, Al-Siyabi and Tanira.
PY - 2016
Y1 - 2016
N2 - Calcium channel blockers (CCBs) are widely used to treat cardiovascular disease (CVD) including hypertension. As aging is an independent risk factor for CVD, the use of CCBs 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 (0.1 nM-1 μM), verapamil (0.1 nM-10 μM), or diltiazem (0.1 nM-10 μM). Relaxation-concentration response curves produced by cumulative concentrations of three different CCBs in arteries of old rats were shifted to the right with statistically significant IC50s. pIC50 ± 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 phenylephrine and reversed by sodium nitroprusside were not different between young and old groups. However, Bay K 8644 (1 μM) 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.
AB - Calcium channel blockers (CCBs) are widely used to treat cardiovascular disease (CVD) including hypertension. As aging is an independent risk factor for CVD, the use of CCBs 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 (0.1 nM-1 μM), verapamil (0.1 nM-10 μM), or diltiazem (0.1 nM-10 μM). Relaxation-concentration response curves produced by cumulative concentrations of three different CCBs in arteries of old rats were shifted to the right with statistically significant IC50s. pIC50 ± 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 phenylephrine and reversed by sodium nitroprusside were not different between young and old groups. However, Bay K 8644 (1 μM) 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.
KW - Aging
KW - Calcium channel blockers
KW - F344 rats
KW - Mesenteric arteries
KW - Voltage-gated calcium channel
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U2 - 10.3389/fphys.2016.00171
DO - 10.3389/fphys.2016.00171
M3 - Article
C2 - 27242545
AN - SCOPUS:84974588241
SN - 1664-042X
VL - 7
JO - Frontiers in Physiology
JF - Frontiers in Physiology
IS - MAY
M1 - 171
ER -