BACKGROUND: Systemic injections of compounds such as gamma(2)-melanocyte-stimulating hormone (gamma(2)-MSH), which increase sympathetic neurogenic vasoconstriction, may be beneficial in treating hemorrhage-induced hypotension. METHODS: This study characterized (1) the hemodynamic responses elicited by systemic injections of gamma(2)-MSH in pentobarbital-anesthetized hemorrhaged rats, and (2) the hemodynamic responses elicited by the replacement of withdrawn blood in these rats. RESULTS: Controlled hemorrhage (4.8 +/- 0.3 mL/rat at 1.5 mL/min) resulted in a pronounced and sustained fall in mean arterial blood pressure (MAP). The fall in MAP was associated with a reduction in heart rate (HR) and hindquarter (HQR) vascular resistance but no changes in mesenteric (MR) or renal (RR) vascular resistances. Systemic injections of gamma(2)-MSH (10-40 microg/kg, i.v.) produced dose-dependent increases in HR, MAP, and vascular resistances of 20 to 60 s in duration in the hemorrhaged rats. In contrast, injection of the withdrawn blood produced an immediate and sustained increase in MAP, which was associated with a pronounced vasodilation in the hindquarter bed but no changes in MR or RR. CONCLUSIONS: These findings suggest that although gamma(2)-MSH elicits pressor and vasoconstrictor responses in hemorrhaged rats, the bolus injection of this peptide may not in itself be an effective strategy for the sustained restoration of MAP in these rats. Moreover, although blood replacement effectively restores MAP via increases in cardiac output rather than total peripheral resistance, it appears that this manipulation produces an active vasodilation in the hindquarter bed. The possibility that this vasodilation involves a sympathetic neurogenic vasodilator system, which innervates the hindlimb vascular bed but not mesenteric or renal vascular beds, will be discussed.
BACKGROUND: Systemic injections of compounds such as gamma(2)-melanocyte-stimulating hormone (gamma(2)-MSH), which increase sympathetic neurogenic vasoconstriction, may be beneficial in treating hemorrhage-induced hypotension. METHODS: This study characterized (1) the hemodynamic responses elicited by systemic injections of gamma(2)-MSH in pentobarbital-anesthetized hemorrhaged rats, and (2) the hemodynamic responses elicited by the replacement of withdrawn blood in these rats. RESULTS: Controlled hemorrhage (4.8 +/- 0.3 mL/rat at 1.5 mL/min) resulted in a pronounced and sustained fall in mean arterial blood pressure (MAP). The fall in MAP was associated with a reduction in heart rate (HR) and hindquarter (HQR) vascular resistance but no changes in mesenteric (MR) or renal (RR) vascular resistances. Systemic injections of gamma(2)-MSH (10-40 microg/kg, i.v.) produced dose-dependent increases in HR, MAP, and vascular resistances of 20 to 60 s in duration in the hemorrhaged rats. In contrast, injection of the withdrawn blood produced an immediate and sustained increase in MAP, which was associated with a pronounced vasodilation in the hindquarter bed but no changes in MR or RR. CONCLUSIONS: These findings suggest that although gamma(2)-MSH elicits pressor and vasoconstrictor responses in hemorrhaged rats, the bolus injection of this peptide may not in itself be an effective strategy for the sustained restoration of MAP in these rats. Moreover, although blood replacement effectively restores MAP via increases in cardiac output rather than total peripheral resistance, it appears that this manipulation produces an active vasodilation in the hindquarter bed. The possibility that this vasodilation involves a sympathetic neurogenic vasodilator system, which innervates the hindlimb vascular bed but not mesenteric or renal vascular beds, will be discussed.