Effect of aminoguanidine on cardiovascular responses and survival time during blood loss: A study in normotensive and deoxycorticosterone acetate-salt hypertensive rats.

INTRODUCTION: Hemorrhagic shock causes more circulatory disturbances and mortality in hypertensive than normotensive subjects. In the late phase of hemorrhagic shock, nitric oxide (NO) overproduction leads to vascular decompensation. In this study, we evaluated the effect of inducible NO synthase (iNOS) inhibitor, aminoguanidine (AG), on hemodynamic parameters and serum nitrite concentration in decompensated hemorrhagic shock model in normotensive and hypertensive male rats. MATERIALS AND METHODS: Twenty-four male rats were divided into hypertensive and normotensive groups (n = 12 each). Hypertension was induced by subcutaneous injection of deoxycorticoesterone acetate (DOCA), 30 mg/kg in uninephrectomized rats. Decompensated hemorrhagic shock was induced by withdrawing blood until the mean arterial pressure (MAP) reached 40 mmHg. After 120 min, each group was assigned to aminguanidine (100 mg/kg) and control group. Hemodynamic parameters were monitored for next 60 min. Blood samples were taken before and after shock period and 60 min after treatment. Survival rate was monitored for 72 h. RESULTS: Infusion of AG in normotensive animals caused a transient increase in MAP and increase of heart rate, whereas it did not affect those parameters in hypertensive animals. Hemorrhagic shock caused a significant rise in serum nitrite concentration in normotensive and hypertensive rats and infusion of AG did not significantly change it in both groups. No significant differences observed in survival rate between AG-treated and not treated groups. CONCLUSION: It seems that inhibition of iNOS with AG does not have beneficial effects on hemodynamatic parameters and survival rate during decompensated hemorrhagic shock in normotensive and hypertensive animals.

Role of exogenous nitric oxide donor in treatment of decompensated hemorrhagic shock in normotensive and hypertensive rats.

INTRODUCTION: In this study, we investigated the role of exogenous NO donor, sodium nitroprusside (SNP), on hemodynamic responses and survival rate during decompensated hemorrhagic shock in normotensive and hypertensive rat. METHODS: Male wistar rats were divided into normotensive and hypertensive groups (n = 12 each). Then, the animals were subjected to decompensated hemorrhagic shock by withdrawing blood until the mean arterial pressure (MAP) reached to 40 mmHg. After the shock period, the animals were randomly assigned to SNP-treated (0.5 mg/kg) and control groups (n = 6 each). MAP and heart rate (HR) were monitored throughout the experiment and 60 min after the administration of drug. Serum NO concentrations were measured. The survival rate was counted during next 72 h. RESULTS: Infusion of SNP caused no significant changes in MAP and HR in normotensive and hypertensive animals. Hemorrhagic shock increased serum NO concentration and SNP administration reduced serum NO concentration in either normotensive or hypertensive groups. Survival counts during 72 h after experiment did not improve by SNP administration, and there were no significant differences between normotensive and hypertensive groups. CONCLUSION: SNP administration cannot improve hemodynamic responses and survival count during decompensated hemorrhagic shock in normotensive and hypertensive animals.

Hemodynamic responses and serum nitrite concentration during uncontrolled hemorrhagic shock in normotensive and hypertensive rats.

BACKGROUND: We evaluated the effect of hypertension on hemodynamic responses and serum nitrite concentrations in normotensive (NT) and deoxycorticosteron acetate (DOCA)-Salt hypertensive (HT) rats. METHODS: Uncontrolled hemorrhagic shock was induced in NT and HT rats (n=7 each) by preliminary bleed of 25 ml/kg followed by a 75% tail amputation. The mean arterial pressure (MAP), heart rate and serum nitrite were measured pre-hemorrhage and during hemorrhage. RESULTS: Changes in time-averaged MAP after hemorrhage were significantly greater in HT group than NT. After resuscitation, the HT rats failed to restore MAP to baseline level. Serum nitrite level in both groups was significantly increased during shock period. Survival rate of HT animals was lower than NT group, although it was not statistically significant. CONCLUSIONS: Marked reduction of MAP and less improvement after resuscitation suggested the less adaptation of cardiovascular system in HT animals which may interfere with management of these subjects during uncontrolled hemorrhagic shock.

Protective role of selective nitric oxide synthase inhibitor for treatment of decompensated hemorrhagic shock in normotensive and hypertensive rats.

INTRODUCTION: Different vasoactive factors can modulate cardiovascular adaptation to hemorrhagic shock including Nitric Oxide (NO). In this study we investigated the effect of the NO synthase inhibitor for treatment of decompensated hemorrhagic shock in normotensive and hypertensive rats. METHODS: Twenty-four male Wistar rats were divided into two groups: The normotensive and hypertensive groups. Hypertension was induced by the DOCA-Salt method for eight weeks. Then, the animals were given hemorrhagic shock by continuously withdrawing blood until the mean arterial pressure (MAP) reached to 40 mmHg. The animals were maintained in the shock state for 120 minutes. Subsequently, they were randomly assigned to L-NAME-treated and non-treated groups and monitored for 60 minutes. The survival time was recorded. Blood samples were taken before and after the shock and 60 minutes after L-NAME administration. RESULTS: Infusion of L-NAME caused a significant increase in MAP in normotensive animals, however, slightly increased MAP in hypertensive animals. The heart rate did not significantly alter. Hemorrhage caused a marked increase in serum nitrite levels in both groups (P<0.05). L-NAME treatment significantly reduced the serum nitrite concentration in the normotensive group (P<0.05), without any change in the hypertensive group. All animals who received L-NAME treatment survived at the end of experiment. Fifty percent of the hypertensive animals died four hours after the experiment. The 72-hour survival rate was similar in the L-NAME treated groups. CONCLUSION: L-NAME infusion during decompensated hemorrhagic shock plays a protective role in the improvement of hemodynamic responses and short-term survival rate in normotensive animals.

Effects of hypertension on hemodynamic response and serum nitrite concentration during graded hemorrhagic shock in rats.

BACKGROUND: Hypertensive patients have higher morbidity and mortality from hemorrhage. In this study, we investigated hemodynamic responses and serum nitrite concentrations during graded hemorrhagic shock and resuscitation in hypertensive (HT) and normotensive (NT) rats. METHODS: Thirteen male rats were divided into two groups, namely HT (n = 6) and NT (n = 7). Hypertension was induced by deoxycorticosterone acetate (DOCA)-salt method in uninephrectomized rats. After 8 weeks, graded hemorrhagic shock was induced during 34 minutes in four steps separated by 8-minute intervals (totally 16 ml/kg). The animals were kept in this condition for 120 minutes (shock period). Then, they were resuscitated with blood withdrawal. Mean arterial pressure (MAP) and heart rate (HR) were measured throughout the experiment. Blood samples were taken before and after shock induction and at the end of the shock period. RESULTS: HT rats experienced more MAP and HR reduction during the shock period and less improvement of hemodynamic response after resuscitation compared with the NT group (p < 0.05). The survival rate 72 hours post-hemorrhage in the HT group was significantly lower than the NT group (16.7% vs. 71.4%, respectively) (p < 0.05). Serum nitrite level in HT animals was lower than the NT group (2.45 ± 0.18 vs. 3.35 ± 0.26 ΅mol/lit, respectively; p < 0.05). In addition, it increased during the shock period in both NT and HT groups (p > 0.05). CONCLUSIONS: More reduction of MAP after hemorrhagic shock, less improvement of MAP and HR after resuscitation and low survival rate in HT animals suggested the impairment of cardiovascular system adaptation of HT animals during blood loss and it should be considered in management of hypertensive subjects.