Potentiated Sympathetic Nervous and Renin-Angiotensin Systems Reduce Nonlinear Correlation Between Sympathetic Activity and Blood Pressure in Conscious Spontaneously Hypertensive Rats

Abstract

Background-Patients with a reduced nonlinear component of heart rate regulation have a poorer outcome. Methods and Results-We investigated whether a nonlinear correlation between renal sympathetic nerve activity (RSNA) and blood pressure or renal blood flow is reduced in conscious, spontaneously hypertensive rats (SHR) by comparing them with normotensive Wistar-Kyoto rats (WKY). We also determined the linearity and nonlinearity of the correlation in SHR who were given an angiotensin II receptor blocker, candesartan, orally for 2 weeks. The RSNA value was higher in SHR than in WKY, and coherence peaks of transfer function were found at 0.05 and 0.80 Hz (ie, below respiratoryand cardiac-related fluctuations). The coherence (linearity) of the transfer function was significantly higher and gain was smaller in SHR than in WKY. Because mutual information values (linear and nonlinear correlation) were similar in both strains, we found the nonlinear correlation to be lower in SHR than in WKY. Time delay values calculated by the mutual information method demonstrated that RSNA preceded blood pressure and renal blood flow by 0.5 to 1.0 s. In SHR given candesartan, the RSNA value was lower, and the linearity was lower and nonlinearity higher than SHR given vehicle. Conclusions-Linear correlation between RSNA and blood pressure or renal blood flow was higher in SHR than in WKY, whereas the nonlinear correlation was lower. Oral treatment with candesartan increased the nonlinearity and reduced the linearity in SHR. Increased RSNA and the renin-angiotensin system may be responsible for the lower nonlinearity and higher linearity in hypertension. (Circulation. 2002;106:620-625.)

Sympathoinhibition caused by orally administered telmisartan through inhibition of the AT1 receptor in the rostral ventrolateral medulla of hypertensive rats

“…25) mg kg À1 per day) than those in the present study (2 mg kg À1 per day). However, Sakata et al 28 demonstrated that 1 mg kg À1 per day of CAN for 2 weeks causes sympathoinhibition in SHR. Although blood pressure of SHRs in their study is lower than that of the SHRSPs in the present study, and the heart rate of the SHRs were similar to that of the WKY rats in their study, these previous studies suggested that the difference in sympathoinhibition between TLM and CAN in the present study may not be due to the dose of CAN.…”

“…15,[18][19][20] Peripherally administered ARBs also inhibit the central actions of angiotensin II in the brain. [21][22][23][24][25][26][27][28] Furthermore, we demonstrated that orally administered TLM inhibits SNS activation by reducing oxidative stress in the brains of hypertensive rats. 16 However, it has not been determined whether the sympathoinhibition caused by orally administered ARBs is a class effect of ARBs.…”

“…22,24,25,28 Direct inhibition of AT 1 R in the RVLM or other areas of the brain inhibits SNS activation, 15,[18][19][20] and superfusion with CAN decreases the electrophysiological activity of RVLM neurons examined using the patch-clamp technique. 42 In previous studies demonstrating sympathoinhibition caused by orally administered CAN in hypertensive rats, the doses of CAN were greater (4, (ref.…”

“…16,[21][22][23][24][25][26][27][28] We demonstrated that orally administered ARBs reduced oxidative stress in the brains of hypertensive rats 16,27 and that orally administered telmisartan (TLM) inhibits SNS activation in hypertensive rats. 16 These results suggest that orally administered ARBs have the potential to inhibit SNS activation through reduction of oxidative stress via inhibition of AT 1 R in the RVLM.…”

Sudden Cardiac Death from the Perspective of Nonlinear Dynamics

“…We sought to make a mathematical model of the system that meets the three experimental findings: 1) the SNA peaks precede the HR peaks and BP nadirs 24 , 2) the power spectra of the HR shows a 1/f-like relationship between frequency and power 19,20 , and 3) the HR exhibits low-order chaos 18 . Based on the conclusion that our system of interest is chaotic in nature, we modeled the system after a known chaotic electrical circuit, the Chua circuit 25,26 .…”