Effects of Pyridoxalated Hemoglobin Polyoxyethylene Conjugate and Other Hemoglobin‐Related Substances on Arterial Blood Pressure in Anesthetized and Conscious Rats

Abstract

The effects of pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) and other hemoglobin-related substances on arterial blood pressure (ABP) and heart rate (HR) were examined. Infusion of PHP and other hemoglobin-related substances elevated ABP and increased HR. The degree of the increase in ABP and HR did not differ among the groups. There were species' differences in responses to PHP. Pretreatment with various blockers did not abolish the elevation of ABP. The pretreatment of NG-monomethyl-L-arginine dose-dependently reduced the elevation of ABP but did not completely abolish it. PHP also elevated ABP in conscious rats. The magnitude of the ABP elevation was significantly smaller than in the anesthetized rats. Results indicate that inhibition of nitric oxide (NO) might be responsible in part for the elevation of ABP, and the degree of the elevation would be dependent on the degree of contribution of NO to the regulation of ABP.

Haemodynamic response following a 10% topload infusion of HemolinkTM in conscious, anaesthetized and treated spontaneously hypertensive rats

“…Clinical trials are being conducted with these products. One common observation seen in both animal and human studies is the pressor effect following administration of HBOCs ( Hess et al ., 1993 ; Kida et al ., 1995 ; Ulatowski et al ., 1995 ). Since some patients requiring blood tmefusion may have a history of hypertension, it is important to understand the potential haemodynamic interaction between hypertensive subjects and HBOCs.…”

“…In addition, the difference in response between the two strains was also diminished. In the literature, there are only limited studies on the interactions between the haemodynamic response to HBOCs and anaesthetics ( Cole et al ., 1995 ; Kida et al ., 1995 ; Sharma et al ., 1995 ). The animal species, model, type of HBOCs and the anaesthetics used all appear to play roles in the response.…”

“…Of pharmacological effects of HBOCs in animal experiments a commonly observed one is elevation of the blood pressure. The severity of hypertension in experimental animals appears to be product‐, species‐ and model‐dependent ( Przbelski et al ., 1991 ; Hamilton et al ., 1992 ; Hess et al ., 1993 ; Kida et al ., 1995 ). Hemolink TM induced a mild increase in mean arterial pressure in some animal models ( Adamson et al ., 1997 ; Ning et al ., 1999 ), and a small increase in MAP and a reciprocal reduction in heart rate were observed in healthy volunteers in the Phase I clinical trial ( Adamson et al ., 1997 ).…”

Short‐term hypoxic vasodilation in vivo is mediated by bioactive nitric oxide metabolites, rather than free nitric oxide derived from haemoglobin‐mediated nitrite reduction

“…) running at 0.17 mg kg −1 min −1 ; haem‐based NO scavenging, where animals received a continuous infusion (50 mg kg −1 h −1 ) of pyridoxylated haemoglobin poly‐oxoethylene (POE‐Hb) (Kida et al . ).…”

Short-term hypoxic vasodilationin vivois mediated by bioactive nitric oxide metabolites, rather than free nitric oxide derived from haemoglobin-mediated nitrite reduction

“…vii) haem-based NO scavenging, where animals received a continuous infusion (50 mg/kg/h) of pyridoxylated haemoglobin poly-oxoethylene (POE-Hb) (Kida et al, 1995).…”