## 1 Introduction  
In recent years, with the rapid development of radiological diagnosis and angiography, iodized contrast media have become the most widely used reagent in diagnostic angiography and catheter interventional therapy in patients with cardiovascular disease (CVD) [1]. The incidence of CIAKI has concurrently surged, becoming the third most prevalent cause of acute renal injury among hospitalized patients [2]. CIAKI, resulting from the intravascular administration of iodine-based contrast media (CM), is a significant complication in this context [3]. To date, the pathogenesis of CIAKI has not been completely clarified. Previous studies on CIAKI have predominantly focused on the mechanisms by which CM induce damage to renal tubules and tubular epithelial cells. However, research investigating its impact on peritubular capillaries (PTCs) remains limited [4; 5; 6]. Studies have revealed a significant increase in the diameter of PTCs following intravenous injection of CM in mice, indicating that PTCs play a crucial role in the onset and progression of CIAKI [7; 8]. PTCs are secondary capillaries in the kidney, densely distributed around the renal tubules [9]. They serve as the primary nonwishing blood vessels for both the renal tubules and the renal interstitium, with their function being highly dependent on the integrity of the vascular endothelial barrier [10]. Following the intravascular injection of CM, renal peritubular endothelial cells (RPECs) are directly exposed to CM within the plasma. This exposure can trigger inflammation, elevate the production of reactive oxygen species (ROS) in endothelial cells, increase plasma osmotic pressure, and induce hemodynamic changes, all contributing to RPEC injury [11]. Some researchers have suggested that in acute renal failure (ARF), the disruption of the endothelial barrier function in RPECs can cause PTC leakage, reducing perivascular perfusion and impairing the delivery of oxygen and nutrients to renal tubular epithelial cells, thereby compromising renal function [11; 12]. The endothelial barrier primarily consists of adherens junctions (AJs), tight junctions (TJs), and the cytoskeleton [13; 14]. Among these, AJs are more widely distributed and have a stronger influence on microvascular function. AJs are primarily composed of vascular endothelial cadherin (VE-cadherin), catenins, and actin [15]. GTPases of the Rho family, including RhoA, Rac1, and Cdc42, are widely recognized as critical regulators of the actin cytoskeleton and AJs, playing a pivotal role in maintaining the integrity of the endothelial barrier [16; 17]. Based on the critical role of endothelial integrity in the pathogenesis of CIAKI, identifying effective therapeutic agents is crucial. One promising candidate is IMD, a member of the calcitonin gene-related peptide (CGRP) superfamily, which is expressed in various endothelial cells [18]. IMD interacts with the cell membrane receptor complex CRLR/RAMPs, participating in the regulation of numerous physiological and pathological processes, including vasodilation, stabilization of the endothelial barrier, and inhibition of apoptosis [19; 20; 21]. Studies have demonstrated that in endothelial cells, IMD binding to its receptor activates adenylate cyclase, resulting in increased intracellular cAMP levels [22; 23]. This rise in cAMP can subsequently activate Rac1, which plays a crucial role in protecting endothelial cells and maintaining the integrity of the endothelial barrier [13]. In CIAKI, damage to PTCs can impair renal tubular function [24]. Consequently, it is hypothesized that PTC damage significantly contributes to renal impairment in CIAKI, and that IMD may exert renorprotective effects by preserving PTC integrity through the cAMP/Rac1 signaling pathway. Notably, IMD exhibits varying effects on the endothelial barrier in different vascular beds. For instance, in isolated rat lungs and human lung endothelial cells, IMD has been shown to stabilize the endothelial barrier via the cAMP/protein kinase A (PKA) pathway [25; 26].