Different blood pressure responses to opioids in three rat hypertension models: role of the baseline status of sympathetic and renin-angiotensin systems

Opioids interact with sympathetic and renin-angiotensin systems in control of arterial pressure (MAP). Our earlier finding that biphalin, a synthetic enkephalin analogue, decreased MAP in anaesthetized spontaneously hypertensive rats (SHR) prompted us to further explore this action, to get new insights into pathogenesis of various forms of hypertension. Biphalin effects were studied in SHR, uninephrectomized rats on high-salt diet (HS/UNX), and rats with angiotensin-induced hypertension (Ang-iH). Beside MAP, renal and iliac blood flows (RBF, IBF) and vascular resistances were measured. In anaesthetized and conscious SHR biphalin, 300 Îźg h-1kg-1 i.v., decreased MAP by ~10 and ~20 mmHg, respectively (PThe accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Differential action of bradykinin on intrarenal regional perfusion in the rat: waning effect in the cortex and major impact in the medulla

The renal kallikrein–kinin system is involved in the control of the intrarenal circulation and arterial pressure but bradykinin (Bk) effects on perfusion of individual kidney zones have not been examined in detail. Effects of Bk infused into renal artery, renal cortex or medulla on perfusion of whole kidney (RBF, renal artery probe) and of the cortex, outer- and inner medulla (CBF, OMBF, IMBF: laser-Doppler fluxes), were examined in anaesthetized rats. Renal artery infusion of Bk, 0.3–0.6 mg kg−1 h−1, induced no sustained increase in RBF or CBF. OMBF and IMBF increased initially 6 or 16%, respectively; only the IMBF increase (+10%) was sustained. Pre-treatment with l-NAME, 2.4 mg kg−1i.v., prevented the sustained but not initial transient elevation of medullary perfusion. Intracortical Bk infusion, 0.75–1.5 mg kg−1 h−1, did not alter RBF or CBF but caused a sustained 33% increase in IMBF. Intramedullary Bk, 0.3 mg kg−1 h−1, did not alter RBF or CBF but caused sustained increases in OMBF (+10%) and IMBF (+23%). These responses were not altered by pre-treatment with 1-aminobenzotriazole, 10 mg kg−1i.v., a cytochrome P-450 (CYP450) inhibitor, but were prevented or significantly attenuated by l-NAME or intramedullary clotrimazole, 3.9 mg kg−1 h−1, an inhibitor of CYP450 epoxygenase and of calcium-dependent K+ channels (KCa). Thus, cortical vasodilatation induced by Bk is only transient so that the agent is unlikely to control perfusion of the cortex. Bk selectively increases perfusion of the medulla, especially of its inner layer, via activation of the NO system and of KCa channels