Activity In Spontaneously Hypertensive Rats Research Articles

Acoustic noise improves motor learning in spontaneously hypertensive rats, a rat model of attention deficit hyperactivity disorder

The spontaneously hypertensive (SH) rat model of ADHD displays impaired motor learning. We used this characteristic to study if the recently described acoustic noise benefit in learning in children with ADHD is also observed in the SH rat model. SH rats and a Wistar control strain were trained in skilled reach and rotarod running under either ambient noise or in 75dBA white noise. In other animals the effect of methylphenidate (MPH) on motor learning was assessed with the same paradigms. To determine if acoustic noise influenced spontaneous motor activity, the effect of acoustic noise was also determined in the open field activity paradigm.We confirm impaired motor learning in the SH rat compared to Wistar SCA controls. Acoustic noise restored motor learning in SH rats learning the Montoya reach test and the rotarod test, but had no influence on learning in Wistar rats. Noise had no effect on open field activity in SH rats, but increased corner time in Wistar. MPH completely restored rotarod learning and performance but did not improve skilled reach in the SH rat.It is suggested that the acoustic noise benefit previously reported in children with ADHD is shared by the SH rat model of ADHD, and the effect is in the same range as that of stimulant treatment. Acoustic noise may be useful as a non-pharmacological alternative to stimulant medication in the treatment of ADHD.

The carotid body as a putative therapeutic target for the treatment of neurogenic hypertension.

In the spontaneously hypertensive (SH) rat, hyperoxic inactivation of the carotid body (CB) produces a rapid and pronounced fall in both arterial pressure and renal sympathetic nerve activity (RSA). Here we show that CB de-afferentation through carotid sinus nerve denervation (CSD) reduces the overactive sympathetic activity in SH rats, providing an effective antihypertensive treatment. We demonstrate that CSD lowers RSA chronically and that this is accompanied by a depressor response in SH but not normotensive rats. The drop in blood pressure is not dependent on renal nerve integrity but mechanistically accompanied by a resetting of the RSA-baroreflex function curve, sensitization of the cardiac baroreflex, changes in renal excretory function and reduced T-lymphocyte infiltration. We further show that combined with renal denervation, CSD remains effective, producing a summative response indicative of an independent mechanism. Our findings indicate that CB de-afferentation is an effective means for robust and sustained sympathoinhibition, which could translate to patients with neurogenic hypertension.

Prolonged renal sympathoinhibition following sustained elevation in arterial pressure

We tested the hypothesis that sustained elevations in mean arterial pressure (MAP) would produce an abbreviated suppression of renal sympathetic nerve activity (RSNA) in spontaneously hypertensive (SH) compared with Wistar-Kyoto (WKY) normotensive rats. For this purpose, we recorded RSNA during and after a 30-min elevation in MAP. Elevations in MAP (35-40 mmHg) induced by phenylephrine resulted in a suppression of RSNA in SH and WKY rats that persisted after MAP had returned to control levels. The prolonged suppression of RSNA was eliminated following sinoaortic denervation, indicating that this response was dependent on afferent baroreceptor mechanisms. The simultaneous recording of RSNA and aortic depressor nerve (ADN) activity provided additional evidence that baroreceptor afferents contribute to this prolonged suppression of RSNA in SH rats. Despite the return of MAP to control levels following the sustained pressure elevation in SH rats, there was a paradoxical increase in ADN activity (39 +/- 14%) compared with control values. In contrast, both ADN activity and MAP returned to control levels in WKY rats following the sustained pressure elevation. The sustained increase of ADN activity in SH rats did not account for the entire magnitude of the prolonged recovery of RSNA. In summary, both SH and WKY rats exhibit prolonged suppression of RSNA, whereas ADN activity is paradoxically elevated in only SH rats following a sustained elevation in MAP.

Chronic effects of arotinolol (S-596) in spontaneously hypertensive rats.

Arotinolol (S-596, ARL) is a beta-adrenoceptor blocking drug with weak alpha-adrenoceptor blocking activity, and may be classified into the fourth generation. Antihypertensive effects of ARL were studied for 12 weeks in spontaneously hypertensive (SHR) rats. Propranolol (PPL) was used as the reference drug. ARL (20 and 100 mg/kg per day, p.o.) and PPL (100 mg/kg per day, p.o.) treatments significantly decreased heart rate, within a week after the drug treatments had started and thereafter. Tail blood pressure (BP), determined by prewarming the rat at 50 degrees C for 3 min, was slightly higher in the two ARL treated groups than in the control. Tail BP was slightly lower in the PPL treated group than in the control. Mean BP determined directly at the 12th week was lower in the two ARL and PPL groups than in the control by more than 20 mmHg. Both ARL (100 mg/kg per day) and PPL (100 mg/kg per day) treatments significantly reduced incidences of the vascular lesions, and also prevented the decrease of kidney weights usually associated with mild vascular lesions. Furthermore, these treatments showed a tendency to decrease plasma renin (PRC) and aldosterone (PAC) concentrations determined 20 h after the last administration. As mean BP must be more reliable than tail BP, it was concluded that ARL (20 and 100 mg/kg per day) showed almost the same chronic antihypertensive activity in SHR rats as PPL (100 mg/kg per day). Preventive effects of ARL on development of vascular lesions also supported the above view.

In vivo study of microvascular wall characteristics and resting control in young and mature spontaneously hypertensive rats.

This study was designed to determine if vessel wall hypertrophy and increased expression of sympathetic activity occur in the microcirculation during the development of hypertension. The cremaster muscle microvasculature of normal Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats was observed at age 5--7 weeks and 16--18 weeks. For age-matched WKY and SHR rats, the diameters, wall thicknesses and vessel wall cross-sectional areas for the majority of comparable types of arterioles were not significantly (p greater than 0.05) different. After denervation of the cremasteric muscle, the large and intermediate diameter arterioles of young WKY rats dilated significantly (p less than 0.05) more than did comparable vessels of SHR rats. In contrast, the dilation of comparable types of arterioles in mature WKY and SHR rats following denervation was not significantly (p greater than 0.05) different. The results do not support either abnormal vessel wall hypertrophy, vasoconstriction or increased expression of sympathetic activity in SHR rats compared to WKY rats up to age 16--18 weeks.