Very low-frequency blood pressure variability depends on voltage-gated L-type Ca²⁺channels in conscious rats

Abstract

Langager AM, Hammerberg BE, Rotella DL, Stauss HM. Very low-frequency blood pressure variability depends on voltage-gated L-type Ca 2ϩ channels in conscious rats. Am J Physiol Heart Circ Physiol 292: H1321-H1327, 2007. First published October 20, 2006; doi:10.1152/ajpheart.00874.2006.-The mechanisms generating highfrequency (HF) and low-frequency (LF) blood pressure variability (BPV) are reasonably well understood. However, little is known about the origin of very low-frequency (VLF) BPV. We tested the hypothesis that VLF BPV is generated by L-type Ca 2ϩ channel-dependent mechanisms. In conscious rats, arterial blood pressure was recorded during control conditions (n ϭ 8) and ganglionic blockade (n ϭ 7) while increasing doses (0.01-5.0 mg ⅐ 100 l Ϫ1 ⅐ h Ϫ1 ) of the L-type Ca 2ϩ channel blocker nifedipine were infused intravenously. VLF (0.02-0.2 Hz), LF (0.2-0.6 Hz), and HF (0.6 -3.0 Hz) BPV were assessed by spectral analysis of systolic blood pressure. During control conditions, nifedipine caused dose-dependent declines in VLF and LF BPV, whereas HF BPV was not affected. At the highest dose of nifedipine, VLF BPV was reduced by 86% compared with baseline, indicating that VLF BPV is largely mediated by L-type Ca 2ϩ channeldependent mechanisms. VLF BPV appeared to be relatively more dependent on L-type Ca 2ϩ channels than LF BPV because lower doses of nifedipine were required to significantly reduce VLF BPV than to reduce LF BPV. Ganglionic blockade markedly reduced VLF and LF BPV and abolished the nifedipine-induced dose-dependent declines in VLF and LF BPV, suggesting that VLF and LF BPV require sympathetic activity to be evident. In conclusion, VLF BPV is largely mediated by L-type Ca 2ϩ channel-dependent mechanisms. We speculate that VLF BPV is generated by myogenic vascular responses to spontaneously occurring perturbations of blood pressure. Other factors, such as sympathetic nervous system activity, may elicit a permissive effect on VLF BPV by increasing vascular myogenic responsiveness. power spectral analysis; myogenic vascular function; nifedipine; autonomic nervous system; ganglionic blockade BLOOD PRESSURE VARIABILITY has received considerable attention during the last decades, not only because enhanced blood pressure variability has been identified as an independent cardiovascular risk factor (33, 35) but also because the patterns of blood pressure variability may provide important insights into cardiovascular regulation (2, 23, 31). Highfrequency (HF) blood pressure variability linked to respiration has been suggested to involve fluctuations in cardiac output of purely mechanical origin (23), secondary to respiratory sinus arrhythmia (2). Low-frequency (LF) blood pressure fluctuations (0.2-0.6 Hz in rats), the so-called Mayer waves (36), have been associated mostly with sympathetic modulation of vascular tone (22, 50, 52). However, very low-frequency (VLF) blood pressure fluctuations (0.02-0.2 Hz in rats) at frequencies below the frequency of Mayer waves are less well understood. A variety of facto...

Blood pressure-renal blood flow relationships in conscious angiotensin II- and phenylephrine-infused rats

“…The BP power at the heartbeat frequency was then calculated within a frequency range centered at the peak between 4 and 8 Hz with its edges defined by the points where the spectral density drops to 1% of the maximum power (27). These frequency bins were selected on the basis of our previous study (27) and their inclusion of various cardiovascular regulatory components (e.g., respiratory, Meyer waves, and myogenic activity) that have been suggested to contribute to BP oscillations (53,72).…”

Tempol-nebivolol therapy potentiates hypotensive effect increasing NO bioavailability and signaling pathway

“…In this context, it is well known that the endothelial-derived NO in rats modulates LF and VLF domains of blood pressure variability [28][29][30]. In fact, spectral analysis of the blood pressure recording suggests that the greater hypotensive response to nebivolol in tempol rats could be attributed to the NO pathway since nebivolol administration induced a reduction of VLF and LF only in the TN group.…”

“…Identification of the frequency components of blood pressure variability by power spectral analysis can potentially provide an approximation about mechanisms involved in blood pressure regulation [28][29][30]. In this context, it is well known that the endothelial-derived NO in rats modulates LF and VLF domains of blood pressure variability [28][29][30].…”

Blood Pressure Variability: Prognostic Value and Therapeutic Implications

“…The frequency components of blood pressure variability (BPV) detected by power spectral analysis include oscillations at the very low frequency (0.02-0.20 Hz in rats and 0.02-0.07 Hz in humans), low-frequency (0.2-0.6 Hz in rats and 0.077-0.15 Hz in humans), and high-frequency domain (1-4 Hz in rats and 0.15-0.40 Hz in humans) ( Table 2) [11]. In this context, while myogenic vascular function, renin angiotensin system, and endothelium-derived NO affect BPV at VLF [8,11], LF variability is modulated by sympathetic modulation of vascular tone and endothelial-derived NO in rats [11]. In addition, normalized LF (LF/HF ratio) has been validated as a marker of sympathetic vascular activity in preclinical and clinical studies [9,10].…”

“…Different mechanisms can contribute in the increase of beatto-beat BPV, including enhanced central sympathetic drive, reduced arterial or cardiopulmonary baroreflex, humoral and rheological factors, behavioral and emotional mechanisms, and changes in ventilation [13]. Beat-to-beat BPV has been used for the study of the mechanism of action of antihypertensive drugs and the diagnosis and treatment of patients with cardiovascular diseases [8,9,11]. For instance, in our laboratory, we have shown that carvedilol induced a greater hypotensive response in spontaneously hypertensive rats in comparison with normotensive control animals [14].…”