Participation of 5-HT and AT1 Receptors within the Rostral Ventrolateral Medulla in the Maintenance of Hypertension in the Goldblatt 1 Kidney-1 Clip Model

الملخص EN

The hypothesis that changes in neurotransmission within the rostral ventrolateral medulla (RVLM) are important to maintain the high blood pressure (BP) was tested in Goldblatt one kidney-one clip hypertension model (1K-1C).

Male Wistar rats were anesthetized (urethane 1.2 g/kg, i.v.), and the effects of bilateral microinjections into the RVLM of the following drugs were measured in 1K-1C or control groups: glutamate (0.1 mol/L, 100 nL) and its antagonist kynurenic acid (0.02 mol/L, 100 nL), the angiotensin AT1 receptor antagonist candesartan (0.01 mol/L, 100 nL), and the nonselective 5-HT receptor antagonist methiothepin (0.06 mol/L, 100 nL).

Experiments in 1K-1C rats were performed 6 weeks after surgery.

In anesthetized rats glutamate response was larger in hypertensive than in normotensive rats (H: Δ67±6.5; N: Δ43±3.54 mmHg).

In contrast, kynurenic acid microinjection into the RVLM did not cause any change in BP in either group.

The blockade of either AT1 or 5-HT receptors within the RVLM decreased BP only in 1K-1C rats.

A largest depressor response was caused by 5-HT receptor blockade.

The data suggest that 5-HT and AT1 receptors act tonically to drive RVLM in 1K-1C rats, and these actions within RVLM contribute to the pathogenesis of this model of hypertension.