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Altered K ATP Channel Subunits Expression and Vascular Reactivity in Spontaneously Hypertensive Rats With Age

View Article: PubMed Central - PubMed

ABSTRACT

ATP-sensitive potassium (KATP) channels link membrane excitability to metabolic state to regulate a series of biological activities including the vascular tone. However, their ability to influence hypertension is controversial. Here we aim to investigate possible alteration of KATP channel in vascular smooth muscles (VSMs) during hypertension development process. In this study, we used 16-week-old spontaneously hypertensive rats (SHRs), 49-week-old SHRs, and their age-matched Wistar-Kyoto rats to study the expression of VSM KATP subunits at the mRNA and protein level and the function of VSM KATP by observing the relaxation reactivity of isolated aorta rings to KATP modulators. We found that the expression of VSM KATP subunits Kir6.1 and sulfonylurea receptor (SUR2B) decreased during hypertension. Moreover, the expression of SUR2B and Kir6.1 in 49-week-old SHRs decreased much more than that in 16-week-old SHRs. Furthermore, the aorta rings of 49-week-old SHRs showed lower reactivity to diazoxide than 16-week-old SHRs. This study suggests that KATP channels in VSM subunits Kir6.1 and SUR2B contribute to modify the functionality of this channel in hypertension with age.

No MeSH data available.


Relative expression of Kir6.1, Kir6.2, SUR2A, and SUR2B mRNA. A, Kir6.1, (B) SUR2B, (C) Kir6.2, and (D) SUR2A. Data shown are the means ± standard error of the mean of 6 separate experiments. *P < 0.05 for the SHR group compared with the respective WKY controls. #P < 0.05 for the 49-week-old SHR group compared with the 16-week-old SHR group.
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Figure 2: Relative expression of Kir6.1, Kir6.2, SUR2A, and SUR2B mRNA. A, Kir6.1, (B) SUR2B, (C) Kir6.2, and (D) SUR2A. Data shown are the means ± standard error of the mean of 6 separate experiments. *P < 0.05 for the SHR group compared with the respective WKY controls. #P < 0.05 for the 49-week-old SHR group compared with the 16-week-old SHR group.

Mentions: In aorta smooth muscle, the mRNA expression of Kir6.1 subunits was decreased by 35% in 16-week-old SHRs (0.65 ± 0.11) when compared with 16-week-old controls (1.00 ± 0.16, P < 0.05). Moreover, it was decreased to an even lower extent of 38% in 49-week-old SHRs (0.49 ± 0.11) compared with 49-week-old controls (0.79 ± 0.08, P < 0.05). Furthermore, compared with 16-week-old SHRs, there was a reduction of about 25% in 49-week-old SHRs. Similarly, VSM mRNA expression of KATP SUR2B subunits showed a 26% reduction in 16-week-old SHRs (0.74 ± 0.06) when compared with 16-week-old controls (1.00 ± 0.11, P < 0.05), and a further reduction of 61% in 49-week-old SHRs (0.36 ± 0.14) compared with 49-week-old controls (0.92 ± 0.18, P < 0.05). Moreover, SUR2B subunits were decreased by 51% in 49-week-old SHRs when compared with 16-week-old SHRs (P < 0.05). However, there were no differences in the Kir6.2 and SUR2A of the mRNA expression between 16-week-old and 49-week-old SHRs when compared with their respective controls (Figs. 2A–D).


Altered K ATP Channel Subunits Expression and Vascular Reactivity in Spontaneously Hypertensive Rats With Age
Relative expression of Kir6.1, Kir6.2, SUR2A, and SUR2B mRNA. A, Kir6.1, (B) SUR2B, (C) Kir6.2, and (D) SUR2A. Data shown are the means ± standard error of the mean of 6 separate experiments. *P < 0.05 for the SHR group compared with the respective WKY controls. #P < 0.05 for the 49-week-old SHR group compared with the 16-week-old SHR group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4979625&req=5

Figure 2: Relative expression of Kir6.1, Kir6.2, SUR2A, and SUR2B mRNA. A, Kir6.1, (B) SUR2B, (C) Kir6.2, and (D) SUR2A. Data shown are the means ± standard error of the mean of 6 separate experiments. *P < 0.05 for the SHR group compared with the respective WKY controls. #P < 0.05 for the 49-week-old SHR group compared with the 16-week-old SHR group.
Mentions: In aorta smooth muscle, the mRNA expression of Kir6.1 subunits was decreased by 35% in 16-week-old SHRs (0.65 ± 0.11) when compared with 16-week-old controls (1.00 ± 0.16, P < 0.05). Moreover, it was decreased to an even lower extent of 38% in 49-week-old SHRs (0.49 ± 0.11) compared with 49-week-old controls (0.79 ± 0.08, P < 0.05). Furthermore, compared with 16-week-old SHRs, there was a reduction of about 25% in 49-week-old SHRs. Similarly, VSM mRNA expression of KATP SUR2B subunits showed a 26% reduction in 16-week-old SHRs (0.74 ± 0.06) when compared with 16-week-old controls (1.00 ± 0.11, P < 0.05), and a further reduction of 61% in 49-week-old SHRs (0.36 ± 0.14) compared with 49-week-old controls (0.92 ± 0.18, P < 0.05). Moreover, SUR2B subunits were decreased by 51% in 49-week-old SHRs when compared with 16-week-old SHRs (P < 0.05). However, there were no differences in the Kir6.2 and SUR2A of the mRNA expression between 16-week-old and 49-week-old SHRs when compared with their respective controls (Figs. 2A–D).

View Article: PubMed Central - PubMed

ABSTRACT

ATP-sensitive potassium (KATP) channels link membrane excitability to metabolic state to regulate a series of biological activities including the vascular tone. However, their ability to influence hypertension is controversial. Here we aim to investigate possible alteration of KATP channel in vascular smooth muscles (VSMs) during hypertension development process. In this study, we used 16-week-old spontaneously hypertensive rats (SHRs), 49-week-old SHRs, and their age-matched Wistar-Kyoto rats to study the expression of VSM KATP subunits at the mRNA and protein level and the function of VSM KATP by observing the relaxation reactivity of isolated aorta rings to KATP modulators. We found that the expression of VSM KATP subunits Kir6.1 and sulfonylurea receptor (SUR2B) decreased during hypertension. Moreover, the expression of SUR2B and Kir6.1 in 49-week-old SHRs decreased much more than that in 16-week-old SHRs. Furthermore, the aorta rings of 49-week-old SHRs showed lower reactivity to diazoxide than 16-week-old SHRs. This study suggests that KATP channels in VSM subunits Kir6.1 and SUR2B contribute to modify the functionality of this channel in hypertension with age.

No MeSH data available.