REDUCED BAROREFLEX SENSITIVITY AND BLUNTED ENDOGENOUS NITRIC OXIDE SYNTHESIS PRECEDE THE DEVELOPMENT OF HYPERTENSION IN TGR(mREN2)27 RATS

Abstract

Transgenic TGR(mREN2)27 (TGR) rats are an animal model of fulminant hypertension characterized by an inverse circadian blood pressure profile. The present study addressed the contribution of nitric oxide (NO) synthesis and baroreflex function to hypertension and the inverse blood pressure pattern. NO synthesis was measured at four different times of day indirectly by excretion of NO metabolites (NOx: NO2- and NO3-) in the urine of 5- and 11-week-old TGR and Sprague-Dawley (SPRD) controls. Blood pressure, heart rate, and motor activity were recorded in age-matched rats of both strains using an implantable telemetry system. Beat-to-beat recording of blood pressure and pulse interval was performed hourly in 6-week-old animals over 24 h. From these data, baroreflex sensitivity (BRS) was calculated by linear regression of spontaneous fluctuations of blood pressure and corresponding changes of pulse interval. Baroreflex sensitivity was lower in pre-hypertensive TGR rats than in SPRD rats, and the reduction was restricted to the daily resting period. In both strains, NOx excretion showed circadian rhythmicity, with peak values during the activity period at night. Interestingly, excretion of NOx was reduced during the resting period in 5-week-old TGR rats prior to the development of hypertension. Impairment of NO synthesis and baroreflex function precede the development of hypertension in TGR rats. The reduction of both parameters was restricted to the resting period and, therefore, could be involved in the development of the inverse circadian blood pressure profile of TGR rats.

Baroreflex sensitivity varies during the rat estrous cycle: role of gonadal steroids

“…The present results confirm the diurnal variations in MAP, HR, and BRS previously observed in male rats; during the dark phase, MAP and HR increase, whereas BRS declines (7,38,57). A new finding is that OVX reduced the light-dark variation in MAP and HR and abolished the circadian rhythm in BRS.…”

Resetting blood pressure by a closed-loop implanted chip system in normotensive rats

“…It is well known that arterial baroreceptor reflex function was impaired in human spontaneous hypertension and in experimental hypertension, as exemplified by a resetting of the baroreflex to a higher level and a decrease in its gain (Borgonio et al, 2001;Mussalo et al, 2002;Gao et al, 2004). Therefore, we invented a chip system based on the theory of set point to control blood pressure, which established an artificial set point by modifying the original set point.…”

Angiotensin peptides and central autonomic regulation

“…Blockade of nitric oxide in the nTS impairs reflex function under normoxic conditions [58]. A reduction in nitric oxide reportedly precedes the development of hypertension and the BRS impairment in (mRen2)27 rats [59]. In the isolated working heart-brain preparation, release of nitric oxide from the vascular endothelium by Ang II increases GABA causing impairment of BRS through suppression of glutamate transmission in the nTS [60].…”