Effects of Intravenous Perfusion of Glucagon on Renal Blood Flow in Conscious Sheep

Abstract

The effect of glucagon on renal haemodynamics in sheep is controversial. In this study we have examined the effects of perfused glucagon on renal blood flow (RBF) in six conscious sheep bilaterally implanted with transit‐time ultrasonic flow metering probes around the renal arteries. Glucagon was perfused intravenously over 90 min at doses of 3.12, 6.25, 12.5, 25, 50 and 100 ng kg−1 min−1. Mean RBF was calculated over 10 min periods. Blood samples were taken to monitor the time course of the changes in glycaemia and glucagonaemia. The perfusions of glucagon induced rapid and progressive dose‐dependent increases in RBF (9‐19.2 %, P < 0.05) and glycaemia (29‐155 %, P < 0.05) for doses of 25‐100 ng kg−1 min−1. High positive correlations were found between the increases in RBF and glucagonaemia (R2= 0.95) and between the increases in RBF and glycaemia (R2= 0.96). At the lowest doses of glucagon (3.12‐12.5 ng kg−1 min−1), the increase in RBF was highly significant; however, the rise in glucose level was not. At the highest doses (25‐100 ng kg−1 min−1) the time course of the changes in RBF was parallel to that of glucagonaemia throughout the perfusion time. However, between minutes 45 and 90 of the glucagon perfusion, the increase in RBF was the inverse of the change in glycaemia, which decreased. One hour after the end of the 50 and 100 ng kg−1 min−1 perfusions, the glucose levels were still significantly higher than the baseline, while the RBF values were not. These results are consistent with the idea that the enhanced RBF cannot be attributed to a rise in blood glucose level. They also show that the haemodynamic response to glucagon perfusion was more sensitive than the metabolic response. It is concluded that the intravenous perfusion of physiological doses of glucagon induced a highly sensitive dose‐dependent increase in RBF in sheep.

Circadian rhythm of renal blood flow in caged sheep. Influence of eating and rumination

“…Glucagon should not be excluded as a possible mediator considering a. that the circadian rhythm of its pancreatic release depends on feeding behaviour in monogastric animals (Ruiter et al, 2003), b. that amino acids increased the glucagonaemia in sheep (Kuhara et al, 1991) and c. that the intravenous infusion of physiological doses of glucagon induced a highly sensitive dose-dependent increase in RBF in sheep (Denis et al, 2003). In anyway, it must be kept in mind that present results cannot be extrapolated to grazing sheep because of their natural continuous feeding behaviour.…”

Lack of glucagon receptor signaling and its implications beyond glucose homeostasis

“…Glucagon exerts a positive effect on renal blood flow and glomerular filtration rate, and increases sodium, chloride, potassium, and inorganic phosphorus clearance ratios (Elrick et al 1958, Bailly et al 1980, Denis et al 2003. No major alterations in renal function have been described in Gcgr K/K mouse models.…”

The effect of intravenous insulin infusion on renal blood flow in conscious sheep is partially mediated by nitric oxide but not by prostaglandins1

“…A possible explanation for this is that the meal-associated increase in RBF could be determined not only by insulin, but also by other vasoactive substances with possible additive effects, such as glucagon, another important glucoregulatory hormone in ruminants. It has been shown that in sheep fed 1 to 3 times daily, plasma glucagon increased af-ter meals (Bassett, 1972;Mineo et al, 1990), and in a previous work, we found that glucagon infusions at physiological doses elicited dose-dependent increases in sheep RBF (Denis et al, 2003). In spite of the known insulin-induced sympathetic activation in both animals and humans (reviewed by Scherrer and Sartori, 1997), HI infusion did not Increase blood pressure, probably because the sympathetic pressor effects were offset by peripheral vasodilatation, as proposed in dogs (Reikerâs and Gunnes, 1986) and humans (Scherrer et al, 1994).…”

“…After experimental procedures, the implanted probes were validated for zero blood flow and calibrated in situ to verify the identity between the real (pumped) and the measured flows, according to the method of D' Almeida et al (1995) and described in a previous work (Denis et al, 2003). If necessary, measured flows were corrected for the slight difference between the true and the read flow rate during calibration.…”