Renal effects of gastrin C‐terminal tetrapeptide (as pentagastrin) and cholecystokinin octapeptide in conscious rabbit and man

Abstract

1 Pentagastrin and cholecystokinin octapeptide (CCK8) were infused i.v. at three different doses in two sets of 4 conscious rabbits following a repeated measurements design (130, 1,300 and 13,000 pmol kg-' min-' pentagastrin; 5, 50 and 450 pmol kg-' min-' CCK8). In man, two different doses of pentagastrin (13 and 65 pmol kg-' min-') were infused in two groups of 6 subjects, and CCK8 (2 pmol kg-' min-') in a third group. According to published human postprandial levels, plasma CCK8-like immunoreactivity concentrations were supraphysiological at all doses infused. 2 In the rabbit, pentagastrin produced a dose-related fall in urine flow and free water clearance, but no significant change in systemic and renal haemodynamics, electrolyte excretion and measured plasma constituents; however, in human subjects, pentagastrin increased renal sodium excretion and reduced potassium excretion but did not change glomerular filtration rate. 3 In the rabbit, CCK8 produced a dose-related fall in plasma renin activity, plasma calcium concentration and mean arterial blood pressure; dose-dependent increases in effective renal plasma flow, glomerular filtration rate and renal sodium excretion. In man, changes in sodium and potassium excretion similar to pentagastrin were observed; there were no significant changes in plasma renin activity, plasma calcium concentration, blood pressure, effective renal plasma flow or glomerular filtration rate. 4 The pharmacological renal effects of pentagastrin in conscious water-loaded rabbits resemble vasopressin. In contrast, CCK8's most striking effect was vasodilatation and was unusual in inhibiting rather than stimulating renin release. In man the net changes in urine composition found during infusion of these peptides are similar to those produced by the potassium-sparing diuretics, amiloride and triamterene. However the generally weak renal effects observed, even at pharmacological doses, indicate that these peptides are unlikely to influence renal function under normal physiological conditions.

Renal sympathoinhibitory and regional vasodilator responses to cholecystokinin are altered in obesity‐related hypertension

“…Cholecystokinin also inhibits renal sympathetic vasomotor nerve activity via a vagal afferent mechanism (Koyama et al 1990). These sympathoinhibitory effects may play a role in the events that occur after a meal, increasing blood flow to the gut and kidney, to facilitate digestion and to deal with the additional fluid load, respectively (Calam et al 1987; Sartor & Verberne, 2002, 2008, 2010). The role of gut hormones in sympathetic withdrawal of vasomotor tone to these regions is likely to be important, because feeding can increase splanchnic blood flow as much as 150% and renal blood flow up to 100% from baseline (Premen, 1988), and collectively, these vascular beds can command more than half of the total cardiac output postprandially (Echtenkamp et al 1983).…”

CCK as a modulator of cardiovascular function

“…In the absence of anaesthesia, pressor responses and sympathetically mediated generalised vasoconstriction have consistently been reported following systemic administration of CCK in conscious rats, dogs and guinea pigs (Bunting et al, 1997;Fossa et al, 1997;Janssen et al, 1991;Koszycki et al, 1998;Watanabe et al, 2004;Webb et al, 1996) although in rabbits, blood pressure fell (Calam et al, 1987). Tachycardia also accompanied the pressor response evoked in conscious dogs (Fossa et al, 1997;Janssen et al, 1991) although bradycardia was observed in guinea pigs (Fossa et al, 1997).…”

Evidence for CCKB receptors in the guinea-pig kidney: localization and characterization by [125I]gastrin binding studies and by RT-PCR

“…It is interesting to note that previous studies suggested an effect of CCK-related peptides in the kidney. Specifically, it has been shown that CCK-8, which interacts with CCK B receptors with high affinity, is able to cause changes in the glomerular filtration rate and in the renal blood flow in rabbit or man (Calam et al 1987;Duggan et al 1988;Unwin et al 1990). Studies using free-flow renal micropuncture in rats revealed that CCK-8 directly inhibits sodium and water transport in the loop of Henle (Unwin et al 1988).…”