Limits...
Altered β1-3-adrenoceptor influence on α2-adrenoceptor-mediated control of catecholamine release and vascular tension in hypertensive rats.

Berg T - Front Physiol (2015)

Bottom Line: The present study tested if α2AR dysfunctions resulted from altered α2AR/βAR interaction.Inhibition of cAMP-degradation with milrinone and β3AR agonist (BRL37344) enhanced the effect of L-659,066 on release of both catecholamines in SHR and epinephrine in WKY. β1/2AR antagonists and BRL37344 opposed the L-659,066-dependent elimination of the TPR-response to tyramine in WKY. α2AR/βAR antagonists had little influence on the TPR-response in SHR.Selective agonist provoked β3AR-Gi signaling and influenced the tyramine-induced TPR-response in WKY and catecholamine release in SHR.

View Article: PubMed Central - PubMed

Affiliation: Division of Physiology, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo Oslo, Norway.

ABSTRACT

Unlabelled: α2- and β-adrenoceptors (AR) reciprocally control catecholamine release and vascular tension. Disorders in these functions are present in spontaneously hypertensive rats (SHR). The present study tested if α2AR dysfunctions resulted from altered α2AR/βAR interaction. Blood pressure (BP) was recorded through a femoral artery catheter and cardiac output by an ascending aorta flow probe. Total peripheral vascular resistance (TPR) was calculated. Norepinephrine release was stimulated by a 15-min tyramine-infusion, which allows presynaptic release-control to be reflected as differences in overflow to plasma. Surgical stress activated some secretion of epinephrine. L-659,066 (α2AR-antagonist) enhanced norepinephrine overflow in normotensive controls (WKY) but not SHR. Nadolol (β1+2) and ICI-118551 (β2), but not atenolol (β1) or SR59230A [β(3)/1L ] prevented this increase. All βAR antagonists allowed L-659,066 to augment tyramine-induced norepinephrine overflow in SHR and epinephrine secretion in both strains. Inhibition of cAMP-degradation with milrinone and β3AR agonist (BRL37344) enhanced the effect of L-659,066 on release of both catecholamines in SHR and epinephrine in WKY. β1/2AR antagonists and BRL37344 opposed the L-659,066-dependent elimination of the TPR-response to tyramine in WKY. α2AR/βAR antagonists had little influence on the TPR-response in SHR. Milrinone potentiated the L-659,066-dependent reduction of the TPR-response to tyramine.

Conclusions: β2AR activity was a required substrate for α2AR auto inhibition of norepinephrine release in WKY. β1+2AR opposed α2AR inhibition of norepinephrine release in SHR and epinephrine secretion in both strains. βAR-α2AR reciprocal control of vascular tension was absent in SHR. Selective agonist provoked β3AR-Gi signaling and influenced the tyramine-induced TPR-response in WKY and catecholamine release in SHR.

No MeSH data available.


Related in: MedlinePlus

The effect of α2AR-antagonist on the βAR-influence on the HR-response to tyramine-induced norepinephrine release in WKY and SHR. The rats were pre-treated with the peripherally restricted α2AR antagonist L-659,066, alone or combined with βAR antagonist, as indicated by symbol legends. Significant responses (* within symbol) and differences between groups after 15 min (brackets right of curves) were located as indicated. Comparisons were made between the control and the experimental groups, and between corresponding L-659,066 and βAR antagonist + L-659,066 groups. Baselines prior to tyramine are shown in Table 1. *P ≤ 0.05 after curve evaluation (please see Materials and Methods for details).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4403294&req=5

Figure 8: The effect of α2AR-antagonist on the βAR-influence on the HR-response to tyramine-induced norepinephrine release in WKY and SHR. The rats were pre-treated with the peripherally restricted α2AR antagonist L-659,066, alone or combined with βAR antagonist, as indicated by symbol legends. Significant responses (* within symbol) and differences between groups after 15 min (brackets right of curves) were located as indicated. Comparisons were made between the control and the experimental groups, and between corresponding L-659,066 and βAR antagonist + L-659,066 groups. Baselines prior to tyramine are shown in Table 1. *P ≤ 0.05 after curve evaluation (please see Materials and Methods for details).

Mentions: In agreement with previous studies (Berg et al., 2010; Berg and Jensen, 2013), the tyramine-induced release of norepinephrine activated a transient rise in TPR (Figures 5, 6) and a sustained increase in HR (Figures 7, 8), MBP and CO (not shown) in both strains. Pre-treatment with PTX or L-659,066 eliminated the TPR-response to tyramine in WKY (P ≤ 0.001 compared to WKY controls, P = NS for single curve evaluation), and in SHR reduced the TPR-peak response (P ≤ 0.008), but had no effect on the later response (Figure 5). Milrinone reduced the TPR-peak response in both strains (Figure 5). After pre-treatment with milrinone + L-659,066, the tyramine-induced vasoconstriction was reversed to a vasodilatory response in WKY (P ≤ 0.025 compared to the control and milrinone-only groups at 3 and 15 min), and eliminated in SHR (P = NS, single curve evaluation) (Figure 5). When the β3AR agonist BRL37344 was given prior to L-659,066, the TPR-response to tyramine was higher than that after L-659,066 alone in WKY (P = 0.024 at 15 min) but not different in SHR (Figure 5).


Altered β1-3-adrenoceptor influence on α2-adrenoceptor-mediated control of catecholamine release and vascular tension in hypertensive rats.

Berg T - Front Physiol (2015)

The effect of α2AR-antagonist on the βAR-influence on the HR-response to tyramine-induced norepinephrine release in WKY and SHR. The rats were pre-treated with the peripherally restricted α2AR antagonist L-659,066, alone or combined with βAR antagonist, as indicated by symbol legends. Significant responses (* within symbol) and differences between groups after 15 min (brackets right of curves) were located as indicated. Comparisons were made between the control and the experimental groups, and between corresponding L-659,066 and βAR antagonist + L-659,066 groups. Baselines prior to tyramine are shown in Table 1. *P ≤ 0.05 after curve evaluation (please see Materials and Methods for details).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4403294&req=5

Figure 8: The effect of α2AR-antagonist on the βAR-influence on the HR-response to tyramine-induced norepinephrine release in WKY and SHR. The rats were pre-treated with the peripherally restricted α2AR antagonist L-659,066, alone or combined with βAR antagonist, as indicated by symbol legends. Significant responses (* within symbol) and differences between groups after 15 min (brackets right of curves) were located as indicated. Comparisons were made between the control and the experimental groups, and between corresponding L-659,066 and βAR antagonist + L-659,066 groups. Baselines prior to tyramine are shown in Table 1. *P ≤ 0.05 after curve evaluation (please see Materials and Methods for details).
Mentions: In agreement with previous studies (Berg et al., 2010; Berg and Jensen, 2013), the tyramine-induced release of norepinephrine activated a transient rise in TPR (Figures 5, 6) and a sustained increase in HR (Figures 7, 8), MBP and CO (not shown) in both strains. Pre-treatment with PTX or L-659,066 eliminated the TPR-response to tyramine in WKY (P ≤ 0.001 compared to WKY controls, P = NS for single curve evaluation), and in SHR reduced the TPR-peak response (P ≤ 0.008), but had no effect on the later response (Figure 5). Milrinone reduced the TPR-peak response in both strains (Figure 5). After pre-treatment with milrinone + L-659,066, the tyramine-induced vasoconstriction was reversed to a vasodilatory response in WKY (P ≤ 0.025 compared to the control and milrinone-only groups at 3 and 15 min), and eliminated in SHR (P = NS, single curve evaluation) (Figure 5). When the β3AR agonist BRL37344 was given prior to L-659,066, the TPR-response to tyramine was higher than that after L-659,066 alone in WKY (P = 0.024 at 15 min) but not different in SHR (Figure 5).

Bottom Line: The present study tested if α2AR dysfunctions resulted from altered α2AR/βAR interaction.Inhibition of cAMP-degradation with milrinone and β3AR agonist (BRL37344) enhanced the effect of L-659,066 on release of both catecholamines in SHR and epinephrine in WKY. β1/2AR antagonists and BRL37344 opposed the L-659,066-dependent elimination of the TPR-response to tyramine in WKY. α2AR/βAR antagonists had little influence on the TPR-response in SHR.Selective agonist provoked β3AR-Gi signaling and influenced the tyramine-induced TPR-response in WKY and catecholamine release in SHR.

View Article: PubMed Central - PubMed

Affiliation: Division of Physiology, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo Oslo, Norway.

ABSTRACT

Unlabelled: α2- and β-adrenoceptors (AR) reciprocally control catecholamine release and vascular tension. Disorders in these functions are present in spontaneously hypertensive rats (SHR). The present study tested if α2AR dysfunctions resulted from altered α2AR/βAR interaction. Blood pressure (BP) was recorded through a femoral artery catheter and cardiac output by an ascending aorta flow probe. Total peripheral vascular resistance (TPR) was calculated. Norepinephrine release was stimulated by a 15-min tyramine-infusion, which allows presynaptic release-control to be reflected as differences in overflow to plasma. Surgical stress activated some secretion of epinephrine. L-659,066 (α2AR-antagonist) enhanced norepinephrine overflow in normotensive controls (WKY) but not SHR. Nadolol (β1+2) and ICI-118551 (β2), but not atenolol (β1) or SR59230A [β(3)/1L ] prevented this increase. All βAR antagonists allowed L-659,066 to augment tyramine-induced norepinephrine overflow in SHR and epinephrine secretion in both strains. Inhibition of cAMP-degradation with milrinone and β3AR agonist (BRL37344) enhanced the effect of L-659,066 on release of both catecholamines in SHR and epinephrine in WKY. β1/2AR antagonists and BRL37344 opposed the L-659,066-dependent elimination of the TPR-response to tyramine in WKY. α2AR/βAR antagonists had little influence on the TPR-response in SHR. Milrinone potentiated the L-659,066-dependent reduction of the TPR-response to tyramine.

Conclusions: β2AR activity was a required substrate for α2AR auto inhibition of norepinephrine release in WKY. β1+2AR opposed α2AR inhibition of norepinephrine release in SHR and epinephrine secretion in both strains. βAR-α2AR reciprocal control of vascular tension was absent in SHR. Selective agonist provoked β3AR-Gi signaling and influenced the tyramine-induced TPR-response in WKY and catecholamine release in SHR.

No MeSH data available.


Related in: MedlinePlus