GSNO infusion fcgmin

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Fig. 9. Drop in arterial blood pressure of preeclamptic pregnancies upon infusion of increasing doses of GSNO. (From Ref. [134].)

RSNO has been implicated in a number of respiratory diseases. In ammatory state as in pneumonia gives higher RSNO levels in the lungs. Asthmatic patients exhale high levels of NO but have depressed RSNO levels in the airways. The modulation of RSNO status for clinical therapy is only now being considered [66,70,135].

Injection of modest doses of GSNO has also been found to promote wound healing in rats. In this case, repeated intraperitoneal injection of GSNO was found to accelerate healing of skin lesions by promoting deposition of new collagen in the affected areas [136] (Fig. 10).

External application of RSNO avoids the risk of exceedingly strong vasodilation and life threatening loss of blood pressure. Very promising results have been recently reported for external application of hydrogels containing GSNO to promote skin repair [137].

Table 3 Effect of venal infusion of GSNO on blood circulation parameters of pregnant women with severe preeclampsia. PI and RI are pulsatility and resistance index, respectively. P-selectin expression is a marker for activation of blood platelets and has a value 1.1 ± 0.2% in healthy pregnancies. Adapted from Ref. [134]

Table 3 Effect of venal infusion of GSNO on blood circulation parameters of pregnant women with severe preeclampsia. PI and RI are pulsatility and resistance index, respectively. P-selectin expression is a marker for activation of blood platelets and has a value 1.1 ± 0.2% in healthy pregnancies. Adapted from Ref. [134]

Parameter

Before infusion

During infusion

Mean arterial pressure (mm Hg)

125 ± 5

104 ± 4

Pulse rate (beats/min)

74 ± 6

90 ± 4

Mean uterine artery RI

0.76 ± 0.03

0.70 ± 0.03

Umbilical artery PI

1.9 ± 0.2

1.6 ± 0.2

Fetal thoracic aorta PI

2.5 ± 0.2

2.3 ± 0.2

P-selectin expression (%)

3.0 ± 0.5

1.2 ± 0.2

Fig. 10. Hydroxyproline content of scar tissue at two time points after dorsal incision in rats. Hydroxyproline is the main component of collagen. After incision GSNO and GSH were injected intraperitoneally at 24 h intervals with dose of 0.3 mg/kg. The treatment with GSNO signi cantly enhances the collagen deposition in the affected tissue. (From Ref. [137].)

Fig. 10. Hydroxyproline content of scar tissue at two time points after dorsal incision in rats. Hydroxyproline is the main component of collagen. After incision GSNO and GSH were injected intraperitoneally at 24 h intervals with dose of 0.3 mg/kg. The treatment with GSNO signi cantly enhances the collagen deposition in the affected tissue. (From Ref. [137].)

The bene cial action was attributed to a combination of factors. First, the sterilizing action of NO radicals released from the GSNO. Second, the vasodilation and ensuing improvement of blood supply to the affected tissues.

The older literature on potential therapeutic applications of S-nitrosothiols was reviewed in Refs. [138 140].

Summarizing the above results, it appears surprising that such a powerful vasodilator has found relatively few practical therapeutical applications. As mentioned before, this state of affairs is primarily caused by the practical problems regarding the need to keep complete control over the dosage to avoid life threatening loss of systemic blood pressure. S-nitrosothiols, whether they be of low or high molecular weight, clearly elicit strong physiological responses. Some of these responses are acute (e.g. vasodilation) and some induced on a longer timescale (like apoptosis). But strong that they are and since the S-nitrosothiols are endogenously formed, these compounds deserve constant attention and consideration by researchers in the eld of NO.

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