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Cerebral artery alpha-1 AR subtypes: high altitude long-term acclimatization responses.

Goyal R, Goyal D, Chu N, Van Wickle J, Longo LD - PLoS ONE (2014)

Bottom Line: Following acclimatization to LTH, ovine MCA showed a 20% reduction (n = 5; P<0.05) in the maximum tension achieved by 10-5 M phenylephrine (PHE).Also, our results demonstrate that extracellular regulated kinase 1 and 2 (ERK1/2)-mediated negative feedback regulation of PHE-induced contractility is modulated by α1B-AR subtype.Overall, in ovine MCA, LTH produces profound effects on α1-AR subtype expression and function.

View Article: PubMed Central - PubMed

Affiliation: Center for Perinatal Biology, Department of Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, California, United States of America; Epigenuity LLC, Loma Linda, California, United States of America.

ABSTRACT
In response to hypoxia and other stress, the sympathetic (adrenergic) nervous system regulates arterial contractility and blood flow, partly through differential activities of the alpha1 (α1) - adrenergic receptor (AR) subtypes (α1A-, α1B-, and α1D-AR). Thus, we tested the hypothesis that with acclimatization to long-term hypoxia (LTH), contractility of middle cerebral arteries (MCA) is regulated by changes in expression and activation of the specific α1-AR subtypes. We conducted experiments in MCA from adult normoxic sheep maintained near sea level (300 m) and those exposed to LTH (110 days at 3801 m). Following acclimatization to LTH, ovine MCA showed a 20% reduction (n = 5; P<0.05) in the maximum tension achieved by 10-5 M phenylephrine (PHE). LTH-acclimatized cerebral arteries also demonstrated a statistically significant (P<0.05) inhibition of PHE-induced contractility in the presence of specific α1-AR subtype antagonists. Importantly, compared to normoxic vessels, there was significantly greater (P<0.05) α1B-AR subtype mRNA and protein levels in LTH acclimatized MCA. Also, our results demonstrate that extracellular regulated kinase 1 and 2 (ERK1/2)-mediated negative feedback regulation of PHE-induced contractility is modulated by α1B-AR subtype. Overall, in ovine MCA, LTH produces profound effects on α1-AR subtype expression and function.

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Related in: MedlinePlus

PHE responses in the presence of rho kinase inhibitor (10−5 M Y-27632) and specific α1-AR subtypes antagonists.n = 5 sheep in each group. Values are means ± standard error of means. *Denotes P = <0.05.
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pone-0112784-g010: PHE responses in the presence of rho kinase inhibitor (10−5 M Y-27632) and specific α1-AR subtypes antagonists.n = 5 sheep in each group. Values are means ± standard error of means. *Denotes P = <0.05.

Mentions: As seen in Figure 10, upon application of a Rho kinase inhibitor (10−5 Y-27632), we observed essentially a complete inhibition of PHE-induced contractility in both normoxic and LTH acclimatized MCA. No significant differences were observed in the presence of the several α1-AR subtype inhibitors.


Cerebral artery alpha-1 AR subtypes: high altitude long-term acclimatization responses.

Goyal R, Goyal D, Chu N, Van Wickle J, Longo LD - PLoS ONE (2014)

PHE responses in the presence of rho kinase inhibitor (10−5 M Y-27632) and specific α1-AR subtypes antagonists.n = 5 sheep in each group. Values are means ± standard error of means. *Denotes P = <0.05.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4231100&req=5

pone-0112784-g010: PHE responses in the presence of rho kinase inhibitor (10−5 M Y-27632) and specific α1-AR subtypes antagonists.n = 5 sheep in each group. Values are means ± standard error of means. *Denotes P = <0.05.
Mentions: As seen in Figure 10, upon application of a Rho kinase inhibitor (10−5 Y-27632), we observed essentially a complete inhibition of PHE-induced contractility in both normoxic and LTH acclimatized MCA. No significant differences were observed in the presence of the several α1-AR subtype inhibitors.

Bottom Line: Following acclimatization to LTH, ovine MCA showed a 20% reduction (n = 5; P<0.05) in the maximum tension achieved by 10-5 M phenylephrine (PHE).Also, our results demonstrate that extracellular regulated kinase 1 and 2 (ERK1/2)-mediated negative feedback regulation of PHE-induced contractility is modulated by α1B-AR subtype.Overall, in ovine MCA, LTH produces profound effects on α1-AR subtype expression and function.

View Article: PubMed Central - PubMed

Affiliation: Center for Perinatal Biology, Department of Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, California, United States of America; Epigenuity LLC, Loma Linda, California, United States of America.

ABSTRACT
In response to hypoxia and other stress, the sympathetic (adrenergic) nervous system regulates arterial contractility and blood flow, partly through differential activities of the alpha1 (α1) - adrenergic receptor (AR) subtypes (α1A-, α1B-, and α1D-AR). Thus, we tested the hypothesis that with acclimatization to long-term hypoxia (LTH), contractility of middle cerebral arteries (MCA) is regulated by changes in expression and activation of the specific α1-AR subtypes. We conducted experiments in MCA from adult normoxic sheep maintained near sea level (300 m) and those exposed to LTH (110 days at 3801 m). Following acclimatization to LTH, ovine MCA showed a 20% reduction (n = 5; P<0.05) in the maximum tension achieved by 10-5 M phenylephrine (PHE). LTH-acclimatized cerebral arteries also demonstrated a statistically significant (P<0.05) inhibition of PHE-induced contractility in the presence of specific α1-AR subtype antagonists. Importantly, compared to normoxic vessels, there was significantly greater (P<0.05) α1B-AR subtype mRNA and protein levels in LTH acclimatized MCA. Also, our results demonstrate that extracellular regulated kinase 1 and 2 (ERK1/2)-mediated negative feedback regulation of PHE-induced contractility is modulated by α1B-AR subtype. Overall, in ovine MCA, LTH produces profound effects on α1-AR subtype expression and function.

Show MeSH
Related in: MedlinePlus