A Possible Purinergic Mechanism for Reactive Ischemia in Isolated, Cross-Circulated Rat Kidney

Abstract

Abstract-The isolated kidney of the recipient rat was perfused at a fixed flow rate with blood from a donor by a cross-circulation technique. The renal vasculature responded to the release of arterial occlusion with vasoconstriction, the magnitude of which was increased with increase in the duration of occlusion. ATP, ADP, AMP, adenosine. noradrenaline and 5-HT injected into the renal artery induced a prominent vasoconstriction; IMP and inosine had only a weak vasoconstrictor effect even in large doses. Theophylline reduced the vasoconstriction in response to arterial occlusion and to ATP and adenosine but did not affect that produced by noradrenaline or 5-HT. This suggests that adenine compounds, particularly adenosine, may play a role in the genesis of reactive vasoconstriction after arterial occlusion in the isolated rat kidney.Research on the postocclusive vascular response in the kidney was initiated at the end of the 19th century (1), but the response remains the subject of intensive investigation even at present (2-7).Postocclusive vasoconstriction appears to be a characteristic response of the kidney; it is not observed in other tissues (8-9). It has been suggested that mediator substances such as adenosine (5, 7, 10) or adenosine monophosphate (11) may play a role in the genesis of the vasoconstriction.In the rat isolated, cross-circulated kidney, we attempted to elucidate a possible mecha nism responsible for induction of the postocclusive vasoconstriction. MATERIALS AND METHODSMale Sprague-Dawley rats were allowed free access to food and water overnight before use in the present studies. Surgical procedursDonor rats (550-750 g) were anesthetized with pentobarbital sodium (65 mg/kg i.p.).The right jugular vein and carotid artery were exposed and cannulated by polyethylene cannulae. Heparin sodium (1000 U/kg) was injected and the blood pressure was measured from the left femoral artery with a pressure transducer (Nihon Kohden, MPU-0.5). The carotid and jugular cannulae of the donor rat were connected to the perfusion circuit after the circuit had been filled with 15 ml of blood freshly drawn from heparinized rats.Recipient rats (180-250 g) were anesthetized with pentobarbital sodium (75 mg/kg i.p.). According to the method described by , the right kidney, the right renal artery, the superior mesenteric artery, the abdominal part of the inferior vena cava and the abdominal aorta were exposed through an abdominal incision in the mid-line.

Purinergic Signaling and Blood Vessels in Health and Disease

“…In contrast to most other vessels, extracellular adenosine produces vasoconstriction of the renal vasculature via A 1 receptors and hence is a candidate for the decrease in renal blood flow and gomerular filtration rate that occurs in ischemic kidneys. Theophylline, a P1 adenosine receptor antagonist, reduced the vasoconstriction in response to arterial occlusion and that to adenosine (and ATP) (Sakai et al, 1979b). It was suggested that renal ischemic preconditioning can protect against ischemia-reperfusion injury by decreasing the renal interstitial concentrations of adenosine and ATP, and it was claimed that A 1 receptor activation during ischemia-reperfusion injury is detrimental to renal function .…”

Role of Interstitial ATP and Adenosine in the Regulation of Renal Hemodynamics and Microvascular Function

“…Majid et al (26) demonstrated that pretreatment with a nitric oxide (NO) synthase inhibitor abolished the renal vasodilation caused by intra-arterial infusion of ATP and converted the vasodilatory response to a vasoconstrictor response. On the other hand, intrarenal arterial infusion of ATP resulted in renal vasoconstriction in rabbits (73) and rats (74,75). Further studies in isolated perfused rat kidneys showed that α,β-methylene ATP, which is relatively selective for P2X receptors, caused renal vasoconstriction (76).…”

“…Importantly, RBF responses to exogenously administered ATP are mediated through mechanisms that are distinct from those elicited by adenosine. Sakai et al (75) showed that renal vasoconstriction induced by intrarenal administration of ATP was not sensitive to adenosine receptor blockade. Similarly, Inscho et al (14,19) demonstrated that ATP-mediated vasoconstriction of afferent arterioles was not blocked by adenosine receptor blockade.…”

Development and application of a simple microassay for adenosine in rat plasma.

“…Adenosine has been implicated as a mediator of reactive hyperemia, 1 ' 2 reactive ischemia, 3 regulation of the splanchnic circulation, 4 tubuloglomerular feedback, 5 and renovascular hypertension. 6 In addition, adenosine has been implicated as a modulator of noradrenergic neurotransmission 7 and renin release.…”