Vascular effects of a tripeptide fragment of novokinine in hypertensive rats: Mechanism of the hypotensive action

Abstract Background Activation of angiotensin AT 2 receptors (AT 2 R) counteracts vasoconstrictor effects of AT 1 R stimulation and contributes to blood pressure control. We examined effects on mean arterial pressure (MAP) and renal hemodynamics of LKP, a tripeptide fragment of novokinine, an established AT 2 R agonist. Methods Effects of intravenous LKP infusion and then superimposed losartan (AT 1 R antagonist) on MAP, total renal (RBF, Transonic probe) and renal medullary blood flows (laser-Doppler), and on renal excretion, were examined in anesthetized (1) Wistar rats with acute norepinephrine-induced hypertension, untreated or pretreated with AT 2 R antagonist (PD 123319) and (2) spontaneously hypertensive rats (SHR) maintained on standard or high-sodium (HS) diet. Results In Wistar rats LKP decreased MAP (−4%, p p p Conclusions LKP lowered MAP in norepinephrine-induced hypertension, probably via activation of AT 2 R. At reduced availability of AT 2 R, as in SHR, LKP appeared to bind to different receptors, possibly AT 1 , and induced systemic or renal vasoconstriction. Compared to the parent novokinine, a smaller LKP molecule might be easier absorbed after oral application and more useful in therapy.