Increased baroreceptor response in mice deficient in monoamine oxidase A and B

Abstract

The recent development of mice doubly deficient for monoamine oxidase A and B (MAO-A/B, respectively) has raised questions about the impact of these mutations on cardiovascular function, in so far as these animals demonstrate increased tissue levels of the vasoactive amines serotonin, norepinephrine, dopamine, and phenylethylamine. We recorded femoral arterial pressures and electrocardiograms in adult MAO-A/B-deficient mice during halothane-nitrous oxide anesthesia as well as 30 min postoperatively. During both anesthesia and recovery, systolic, diastolic, and mean arterial pressures were 10-15 mmHg lower in MAO-A/B-deficient mice compared with normal controls (P < 0.01). Mutants also showed a greater baroreceptor-mediated reduction in heart rate in response to hypertension after intravenous pulses of phenylephrine or angiotensin II. Tachycardia elicited in response to hypotension after nitroprusside was greater in mutants than in controls. Heart rate responsiveness to changes in arterial pressure was abolished after administration of glycopyrrolate, with no differences in this phenomenon noted between genotypes. These data suggest that prevention of hypertension may occur in chronic states of catecholaminergic/indoleaminergic excess by increased gain of the baroreflex.

RGS2 Is a Mediator of Nitric Oxide Action on Blood Pressure and Vasoconstrictor Signaling

“…After equivalent baseline blood pressures were established, we administered to each mouse a series of bolus injections containing phenylephrine [PE; 25 g/kg i.v., which increased MAP to 70% of the value obtained with a maximal dose of PE ] alone or in combination with various amounts of sodium nitroprusside (SNP): PE alone, PE ϩ 15 g/kg SNP, and PE ϩ 45 g/kg SNP. These are the lowest effective doses of SNP as established previously (Holschneider et al, 2002). After a given injection exerted its effects on blood pressure and blood pressure values returned to starting baseline values, a subsequent injection was administered.…”

Impaired Baroreflex Function in Mice Overexpressing Alpha-Synuclein

“…Thus, it is unclear at this point whether the functional impairments are associated with either peripheral or central pathology or a combination of both. Functional deficits in central noradrenergic and dopaminergic systems have been observed in this mouse line (23, 24, 42, Maidment and Chesselet, unpublished observations) and dysregulation of central noradrenergic and dopaminergic systems has been shown to alter baroreceptor function in rodents suggesting central catecholamine system dysfunction could be a contributing factor (8, 27). Sodium nitroprusside, in addition to its peripheral vasodilator actions, is also known to activate central noradrenergic neurons in the locus coeruleus (43).…”

Nav2 is necessary for cranial nerve development and blood pressure regulation

“…For the baroreceptor reflex study, mice were anesthetized and then both femoral arteries were catheterized to obtain a continuous recording of pressure and to provide a port to infuse drugs using methods adapted from [61]. The electrical signals from the pressure transducer and EKG electrodes were connected to bridge amplifiers (AstroMed Grass Technologies, Warwick, RI, USA).…”