Article date: February 1995
By: Haroutioun Hasséssian, Geoffrey Burnstock, in Volume 114, Issue 4, pages 846-850
The potentiating effect of NG‐nitro‐l‐arginine methyl ester, (l‐NAME) a nitric oxide synthesis inhibitor, on responses of the rat pulmonary vascular pressure (PVP) to purinoceptor agonists was examined.
At a constant flow of 23 ml min−1 the PVP was 22.4 ± 2.5 mmHg (n = 15), and treatment with 100 μm l‐NAME for 15 min was without effect on the PVP. After the tone was raised with 28 nmol 9,11‐dideoxy‐11α, 9α‐epoxymethano‐prostaglandin F2α (U‐46619), the PVP was 29.4 ± 3.3 mmHg and treatment with 100 μm l‐NAME was still without effect on the PVP. It appears that there is a graded release of nitric oxide in response to different levels of steady shear stress and in our experimental model the threshold for detection was not reached under basal conditions.
In contrast, when the circulation was challenged with 30 s step, additive increases in flow between 11 and 50 ml min−1 (n = 8), treatment with 100 μm l‐NAME produced a significant (P <0.05) increase in PVP suggesting that changes in flow‐derived forces evoke the release of nitric oxide. This was evident for flow rates above 30 ml min−1.
In preparations in which tone was raised with U‐46619, a dose of 1 times 10−8 mol ATP or 2‐meSATP evoked a drop in PVP while α,β‐meATP produced an increase in PVP under constant flow of 23 ml min−1. After treatment with 100 μm l‐NAME, all three purinoceptor agonists evoked an increase in PVP. The increase in PVP evoked by α,β‐meATP was not affected by l‐NAME. These results suggest that P2Y‐purinoceptor stimulation evokes the release of nitric oxide to produce vasodilatation.
Under conditions of constant flow and basal pressure, 100 μm l‐NAME significantly (P <0.05) potentiated the increase in PVP evoked by 1 times 10−6 mol ATP, although the increase evoked by 1 times 10−8 mol α,β‐meATP, which was of similar magnitude, was not affected. These results indicate that a blockade of evoked nitric oxide release is responsible for the potentiation of the increase in PVP evoked by ATP.
This study shows that, while nitric oxide does not appear to be released in the pulmonary circulation of the rat under constant flow conditions, nitric oxide release evoked by purinoceptor agonists attenuates increases in pulmonary vascular pressure.
The potentiating effect of NG‐nitro‐l‐arginine methyl ester, (l‐NAME) a nitric oxide synthesis inhibitor, on responses of the rat pulmonary vascular pressure (PVP) to purinoceptor agonists was examined.
At a constant flow of 23 ml min−1 the PVP was 22.4 ± 2.5 mmHg (n = 15), and treatment with 100 μm l‐NAME for 15 min was without effect on the PVP. After the tone was raised with 28 nmol 9,11‐dideoxy‐11α, 9α‐epoxymethano‐prostaglandin F2α (U‐46619), the PVP was 29.4 ± 3.3 mmHg and treatment with 100 μm l‐NAME was still without effect on the PVP. It appears that there is a graded release of nitric oxide in response to different levels of steady shear stress and in our experimental model the threshold for detection was not reached under basal conditions.
In contrast, when the circulation was challenged with 30 s step, additive increases in flow between 11 and 50 ml min−1 (n = 8), treatment with 100 μm l‐NAME produced a significant (P <0.05) increase in PVP suggesting that changes in flow‐derived forces evoke the release of nitric oxide. This was evident for flow rates above 30 ml min−1.
In preparations in which tone was raised with U‐46619, a dose of 1 times 10−8 mol ATP or 2‐meSATP evoked a drop in PVP while α,β‐meATP produced an increase in PVP under constant flow of 23 ml min−1. After treatment with 100 μm l‐NAME, all three purinoceptor agonists evoked an increase in PVP. The increase in PVP evoked by α,β‐meATP was not affected by l‐NAME. These results suggest that P2Y‐purinoceptor stimulation evokes the release of nitric oxide to produce vasodilatation.
Under conditions of constant flow and basal pressure, 100 μm l‐NAME significantly (P <0.05) potentiated the increase in PVP evoked by 1 times 10−6 mol ATP, although the increase evoked by 1 times 10−8 mol α,β‐meATP, which was of similar magnitude, was not affected. These results indicate that a blockade of evoked nitric oxide release is responsible for the potentiation of the increase in PVP evoked by ATP.
This study shows that, while nitric oxide does not appear to be released in the pulmonary circulation of the rat under constant flow conditions, nitric oxide release evoked by purinoceptor agonists attenuates increases in pulmonary vascular pressure.
DOI: 10.1111/j.1476-5381.1995.tb13281.x
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