The induction of B1 receptors (B1Rs) and desensitization or down-regulation of B2 receptors (B2Rs) as a consequence of the production of endogenous kinins has been termed the autoregulation hypothesis. The latter was investigated using two models based on the rabbit: kinin stimulation of cultured vascular smooth muscle cells (SMCs) and in vivo contact system activation (dextran sulphate intravenous injection, 2 mg kg−1, 5 h). Rabbit aortic SMCs express a baseline population of B1Rs that was up-regulated upon interleukin-1β treatment ([3H]-Lys-des-Arg9-BK binding or mRNA concentration evaluated by RT–PCR; 4 or 3 h, respectively). Treatment with B1R or B2R agonists failed to alter B1R expression under the same conditions. Despite consuming endogenous kininogen (assessed using the kinetics of immunoreactive kinin formation in the plasma exposed to glass beads ex vivo) and producing hypotension mediated by B2Rs in anaesthetized rabbits, dextran sulphate treatment failed to induce B1Rs in conscious animals (RT–PCR in several organs, aortic contractility). By contrast, lipopolysaccharide (LPS, 50 μg kg−1, 5 h) was an effective B1R inducer (kidney, duodenum, aorta) but did not reduce kininogen reserve. We tested the alternate hypothesis that endogenous kinin participate in LPS induction of B1Rs. Kinin receptor antagonists (icatibant combined to B-9858, 50 μg kg−1 of each) failed to prevent or reduce the effect of LPS on B1R expression. Dextran sulphate or LPS treatments did not persistently down-regulate vascular B2Rs (jugular vein contractility assessed ex vivo). The kinin receptor autoregulation hypothesis is not applicable to primary cell cultures derived from a tissue known to express B1Rs in a regulated manner (aorta). The activation of the endogenous kallikrein-kinin system is ineffective to induce B1Rs in vivo in an experimental time frame sufficient for B1R induction by LPS. Keywords: Lipopolysaccharide, kinin-induced vascular contraction, receptor for kinins, contact system activation, vascular smooth muscle cells, interleukin-1 Introduction The kinins (peptides related to bradykinin, BK) are known to activate two types of G protein coupled receptors, termed B1 and B2 (Marceau et al., 1998). Lys-des-Arg9-BK (des-Arg10-kallidin) is the optimal agonist sequence of the human and rabbit B1 receptors (B1Rs), whereas BK and Lys-BK in low concentrations stimulate B2 receptors (B2Rs). While the latter are preformed in a wide variety of cells, a large body of evidence shows that the B1Rs are generally not expressed in normal physiological conditions, but rapidly induced following some types of injury; the cytokine network, mitogen-activated protein (MAP) kinases and specific transcription factors have been implicated in this phenomenon (Deblois et al., 1988; Larrivee et al., 1998; Marceau et al., 1998; Ni et al., 1998; Yang et al., 1998). In several systems pertaining to persistent inflammation, there is a temporal shift of kinin effect mediation from preformed B2Rs to induced B1Rs over several hours or days (e.g., inflammatory hyperalgesia and intestinal inflammation models in rodents) (Kachur et al., 1996; Perkins et al., 1993). This also applies to the oedema induced by exogenous kinin injection into the rat paw (Campos et al., 1995). In the latter system, daily injection of the B2R agonist [Tyr8]BK induces oedema of decreasing amplitude; however, the B1R agonist des-Arg9-BK, initially inert, becomes a powerful inflammatory substance by the end of the protocol. These and other observations suggest a pattern of kinin receptor ‘autoregulation' by the agonists. Agonist-induced temporary desensitization of the B2R, involving receptor phosphorylation and endocytosis, is well documented (Blaukat et al., 1996; Faussner et al., 1998; Pizard et al., 1999), but B2R down-regulation is not defined at the molecular level (protein, mRNA). As for B1R induction, the agonist Lys-des-Arg9-BK has been shown to induce B1Rs (mRNA, protein) in the human cell line IMR-90 (Schanstra et al., 1998). This cell line expresses a certain baseline population of B1R, which may not be representative of normal tissues in vivo; NF-κB binding to some DNA sequences reproduced from the B1R gene promoter was activated by the B1R agonist in these cells. Further, the MAP kinase pathways that were found to determine post-isolation B1R induction in rabbit vascular tissue (Larrivee et al., 1998) may be also activated upon kinin receptor stimulation in HEK 293 cells expressing either recombinant B1 or B2Rs (Naraba et al., 1998). In these cells, either B1R or B2R agonists stimulate the nuclear translocation of the transcription factor AP-1, an effect which is blocked by PD98059, the MEK-1 inhibitor. We and others have produced complementary evidence for the role of an AP-1 site in the B1R gene promoter (Yang et al., 1998; Angers et al., 2000). Ultimately, the full model of autoregulation has been illustrated by Phagoo et al. (1999) based on IMR-90 cells: incubation with BK (100 nM) suppressed 89% of the surface B2Rs in a few minutes, but upregulated B1Rs (2–3 fold) in a few hours. Lys-des-Arg9-BK did not influence the population of B2Rs, but also upregulated B1Rs. The agonists increased the expression of IL-1β in the cells, and the natural IL-1 receptor antagonist, IRA, decreased the induction of B1Rs by BK (Phagoo et al., 1999). Therefore, this ‘autoregulation' model integrates several known or suspected regulatory events (autologous desensitization of B2R, involvement of cytokine, MAP kinases and transcription factors in B1R gene transcriptional control). We have investigated whether intense activation of the endogenous kallikrein-kinin system using dextran sulphate (Kaplan et al., 1998) could result in the definite pattern of kinin receptor regulation described above (desensitization or down-regulation of B2Rs, up-regulation of B1Rs) in the live rabbit. Complementary testing of the autoregulation hypothesis has been performed using primary cultures of rabbit vascular SMCs. In addition, kinin participation in LPS induction of B1Rs has been tested as a secondary objective, as LPS treatment may activate the kallikrein-kinin system in rabbits (Erdos & Miwa, 1968).