Subfornical organ mediates pressor effect of angiotensin: Influence of nitric oxide synthase inhibitors, AT1 and AT2 angiotensin antagonist's receptors

Saad, Wilson Abrão; Camargo, Luiz Antonio de Arruda; Guarda, Ismael Francisco Motta Siqueira; Santos, Talmir Augusto Faria Brizola dos

doi:10.1016/j.jash.2008.04.007

« Previous Next »Journal of the American Society of Hypertension
Volume 2, Issue 5 , Pages 326-331, September 2008

Subfornical organ mediates pressor effect of angiotensin: Influence of nitric oxide synthase inhibitors, AT₁ and AT₂ angiotensin antagonist's receptors

Wilson Abrão Saad, MD
- Basic Institute of Biosciences-UNITAU, Taubaté, São Paulo, Brazil
- Department of Exact and Natural Science UNIARA Araraquara, São Paulo, Brazil
- Department of Physiology and Pathology School of Dentistry, Paulista State University, UNESP Araraquara, São Paulo, Brazil
- Department of Physiology, Federal University of São Carlos, São Paulo, Brazil
- Corresponding author: Wilson Abrão Saad, MD, Department of Physiology and Pathology, School of Dentistry, Paulista State University, UNESP, Rua Humaitá, 1680, 14801-903-Araraquara, São Paulo, Brazil. Tel: +55(16) 3301 6488; fax: +55(16) 3322 0836
Luiz Antonio de Arruda Camargo
- Department of Physiology and Pathology School of Dentistry, Paulista State University, UNESP Araraquara, São Paulo, Brazil
- Department of Physiology, Federal University of São Carlos, São Paulo, Brazil
Ismael Francisco Motta Siqueira Guarda, MD
- Department of Anesthesiology Clinic Hospital State of São Paulo, São Paulo, Brazil
Talmir Augusto Faria Brizola dos Santos
- Basic Institute of Biosciences-UNITAU, Taubaté, São Paulo, Brazil

Received 19 February 2008; accepted 10 April 2008. published online 24 June 2008.

Abstract

We investigated the influence of voltage-dependent calcium channels and nitric oxide (NO) on angiotensin II (ANG II)-pressor effect injected into subfornical organ (SFO). The influence of NO on nifedipine antipressor action has also been studied by utilizing N^W-nitro-L-arginine methyl ester (L-NAME) (20 μg × 0.2 μl⁻¹) a nitric oxide synthase inhibitor (NOSI) and 7-nitroindazole (7-NIT) (20 μg × 0.2 μl⁻¹), a specific neuronal nitric oxide synthase inhibitor (nNOSI). We have also investigated the role of losartan and PD123319, selective ANG II AT₁ and AT₂ receptor nonpeptide antagonists, in the pressor effect of ANG II and in the effect of L-NAME and 7-NIT, injected into the SFO. Adult male Holtzman rats (220 to 280 g) were anesthetized with ketamine (80 mg/kg⁻¹ of body weight) plus xylazine (7 mg/kg⁻¹ of body weight), placed in a stereotaxic apparatus (David Kopf model for rats), and implanted with cannula into the SFO. Direct mean arterial blood pressure (MAP) was recorded in conscious rats in a test cage, without access to food or water. The previously implanted catheter into femoral artery was connected to a Statham (P23 Db) pressure transducer (Statham-Gould, Valley View, OH) coupled to a multichannel recorder (PowerLab Multirecord). MAP increased after ANG II injection. Pre-treatment with nifidipine (50 μg × 0.2 μl⁻¹ or 100 μg × 0.2 μl⁻¹) followed by 25 pmol × 0.2 μl⁻¹ of ANG II, decreased ANG II-pressor effect. L-NAME and 7-NIT increased the elevation in MAP induced by ANG II, which was blocked by the prior injection of nifedipine. The AT₁ angiotensin antagonist losartan injected into the SFO blocked the effect of ANG II and the effects of L-NAME and 7-NIT while PD123319 did not. These results provide evidence that ANG II-pressor effect is influenced by nitrergic pathways that utilize L-type calcium channels in the SFO.