Role of central AT₁ and V₁ receptors in cardiovascular adaptation to hemorrhage in SD and renin TGR rats

Abstract

In acute experiments, intracranially applied angiotensin II and vasopressin elicit significant cardiovascular effects. The purpose of the present study was to find out whether chronic intrabrain elevation of these peptides, occurring in the renin transgenic TGR(mRen2)27 (TGR) rats, results in an alteration of the cardiovascular control. Mean arterial blood pressure (MAP) and heart rate responses to hypovolemia were examined in hypertensive TGR and normotensive Sprague-Dawley (SD) rats under control conditions and during blockade of central AT1 or V1 receptors. Both groups received cerebroventricular infusions of either 1) cerebrospinal fluid ( series 1), 2) AT1 receptors antagonist (AT1ANT, series 2), or 3) V1 receptors antagonist (V1ANT, series 3). Blockade of AT1 and V1 receptors decreased MAP in TGR but not in SD rats. In SD rats, bleeding elicited a similar decrease of MAP in each series and a transient increase of heart rate in series 3. In TGR, hemorrhage caused bradycardia and decrease of MAP, which was greater than in SD rats. Hemorrhagic hypotension in TGR was abolished by V1ANT and bradycardia by V1ANT or AT1ANT. The results demonstrate remarkable differences in cardiovascular adjustment to hemorrhage in SD and TGR rats and provide evidence for enhanced involvement of central V1 and AT1 receptors in the regulation of blood pressure during hypovolemia in TGR. Central V1 vasopressin receptors play a crucial role in eliciting posthemorrhagic hypotension and bradycardia in this strain.

Involvement of arginine vasopressin in endogenous central histamine-induced reversal of critical haemorrhagic hypotension in rats

“…Indeed, centrally released AVP plays a role in eliciting bradycardia and hypotension in hypovolaemia in normotensive Kyoto Wistar [54], Hannover Sprague-Dawley [55] and spontaneously hypertensive rats [56]. The proposed mechanism of the effect may involve potentiation by AVP of the central link of the Bezold-Jarisch reflex [55]. Therefore, further studies are needed to establish the possible effects of the vasopressinergic system on metoprine-induced resuscitating action.…”

Central blockade of vasopressin V1receptors attenuates postexercise hypotension

“…On an alternate day (Ͼ48 h), these procedures were repeated except that the rats received an intracerebroventricular injection of AVP-X (100 ng in 10 l). This dose was selected because several studies (7,15,27,35) have used similar doses or equipotent doses of other AVP V 1-receptor antagonists (31) and reported reductions in the pressor response to centrally applied AVP but not to the pressor response to intravenous AVP. Furthermore, this dose has minimal agonist-like properties (15).…”

Oral simvastatin reduces the hypertensive response to air‐jet stress

“…To exclude peripheral actions of the compounds under investigation, we used the lowest doses of AngII (10 ng) and VP (20 ng) that were sufficient to cause significant hypertensive responses when given i.c.v. but did not affect mean arterial blood pressure (MABP) or heart rate (HR) when infused intravenously . Similarly, we infused 10 μg losartan and 400 ng d(CH 2 ) 5 [Tyr(Me) 2 ,Ala‐NH 2 9 ]VP because these doses have been found to abolish pressor responses to centrally, but not peripherally, administered AngII and VP, respectively …”

“…but did not affect mean arterial blood pressure (MABP) or heart rate (HR) when infused intravenously. 19,24,25 Similarly, we infused 10 lg losartan and 400 ng d(CH 2 ) 5 [Tyr(Me) 2 ,Ala-NH 2 9 ]VP because these doses have been found to abolish pressor responses to centrally, but not peripherally, administered AngII and VP, respectively. 19,26,27 Experimental design For 4 weeks before the measurements, rats were maintained on either tap water (control) or water containing 20 mg/L simvastatin (S20), 40 mg/L simvastatin (S40) or 60 mg/L simvastatin (S60).…”