Daisaku Michikami

Increased vasomotor sympathetic nerve activity and decreased plasma nitric oxide release after head-down bed rest in humans: disappearance of correlation between vasoconstrictor and vasodilator.

We hypothesized that the relationship between resting levels of sympathetic vasoconstrictor nerve traffic and dilator substance nitric oxide (NO) release is altered after exposure to microgravity, resulting in abnormal peripheral resistance. To examine the hypothesis, we assessed muscle sympathetic nerve activity (MSNA) (microneurography), an indicator of NO release (plasma nitrite/nitrate concentrations) and leg vascular resistance (venous occlusion plethysmography) in 20 healthy male volunteers before and after 14 days of 6 degrees head-down bed rest (HDBR), the ground-based analogue of microgravity. MSNA increased, while plasma nitrite/nitrate concentrations decreased after HDBR. A significant positive correlation observed between MSNA and plasma nitrite/nitrate concentrations before HDBR disappeared after HDBR. Leg vascular resistance increased after HDBR. In conclusion, an imbalance between sympathetic vasoconstrictor traffic and NO release might contribute to elevated peripheral vascular resistance following HDBR.

Muscle Sympathetic Nerve Activity Averaged Over 1 Minute Parallels Renal and Cardiac Sympathetic Nerve Activity in Response to a Forced Baroreceptor Pressure Change

Background—Despite the accumulated knowledge of human muscle sympathetic nerve activity (SNA) as measured by microneurography, whether muscle SNA parallels renal and cardiac SNAs remains unknown. Method and Results—In experiment 1, muscle (microneurography, tibial nerve), renal, and cardiac SNAs were recorded in anesthetized rabbits (n=6) while arterial pressure was changed by intravenous bolus injections of nitroprusside (3 &mgr;g/kg) followed by phenylephrine (3 &mgr;g/kg). In experiment 2, the carotid sinus region was vascularly isolated in anesthetized, vagotomized, and aorta-denervated rabbits (n=10). The 3 SNAs were recorded while intracarotid sinus pressure was increased stepwise from 40 to 160 mm Hg in 20-mm Hg increments maintained for 60 seconds each. Muscle SNA averaged over 1 minute was well correlated with renal (r=0.96±0.01, mean±SE) and cardiac (r=0.96±0.01) SNAs in experiment 1 (baroreflex closed-loop condition) and also with renal (r=0.97±0.01) and cardiac (r=0.97±0.01) SNAs in experiment 2 (baroreflex open-loop condition). Conclusions—Muscle SNA averaged over 1 minute parallels renal and cardiac SNAs in response to a forced baroreceptor pressure change.

Resetting of the arterial baroreflex increases orthostatic sympathetic activation and prevents postural hypotension in rabbits

Since humans are under ceaseless orthostatic stress, the mechanism to maintain arterial pressure (AP) under orthostatic stress against gravitational fluid shift is of great importance. We hypothesized that (1) orthostatic stress resets the arterial baroreflex control of sympathetic nerve activity (SNA) to a higher SNA, and (2) resetting of the arterial baroreflex contributes to preventing postural hypotension. Renal SNA and AP were recorded in eight anaesthetized, vagotomized and aortic‐denervated rabbits. Isolated intracarotid sinus pressure (CSP) was increased stepwise from 40 to 160 mmHg with increments of 20 mmHg (60 s for each CSP level) while the animal was placed supine and at 60 deg upright tilt. Upright tilt shifted the CSP–SNA relationship (the baroreflex neural arc) to a higher SNA, shifted the SNA–AP relationship (the baroreflex peripheral arc) to a lower AP, and consequently moved the operating point to marked high SNA while maintaining AP. A simulation study suggests that resetting in the neural arc would double the orthostatic activation of SNA and increase the operating AP in upright tilt by 10 mmHg, compared with the absence of resetting. In addition, upright tilt did not change the CSP–AP relationship (the baroreflex total arc). A simulation study suggests that although a downward shift of the peripheral arc could shift the total arc downward, resetting in the neural arc would compensate this fall and prevent the total arc from shifting downward to a lower AP. In conclusion, upright tilt increases SNA by resetting the baroreflex neural arc. This resetting may compensate for the reduced pressor responses to SNA in the peripheral cardiovascular system and contribute to preventing postural hypotension.

Interrelations of vasoconstrictor sympathetic outflow to skin and core temperature during unilateral sole heating in humans

The purpose of the present study was to clarify how skin sympathetic nerve activity (SSNA) influences the core temperature during local heating of the unilateral sole of the foot for 60 min. We recorded SSNA microneurographically from the tibial or peroneal nerve simultaneously with skin blood flow, sweat rate at heated and non-heated sites, with tympanic temperature (Tty) as the core temperature. Sole heating began to suppress vasoconstrictive SSNA (vasoconstrictor) after 3.4 +/- 1.1 min, decrease Tty after 7.4 +/- 2.0 min, activate vasoconstrictor after 33.4 +/- 2.2 min, and increase Tty after 45.5 +/- 2.7 min. Regarding the interaction between vasoconstrictor and Tty during sole heating, we found the following: (1) the capability to suppress vasoconstrictors (decrease rate) showed positive correlations with the time delay from vasoconstrictor suppression to the Tty decrease (r = 0.752, p < 0.05), and with the Tty decrease rate (r = 0.795, p < 0.05), (2) the Tty decrease rate was inversely related to the capability to activate vasoconstrictors (increase rate) (r= -0.836, p < 0.05), and (3) the capability to activate vasoconstrictors was inversely related to the time delay from vasoconstrictor activation to the Tty increase (r = -0.856, p < 0.05) and showed a positive correlation with the Tty increase rate (r = 0.819, p < 0.05). These significant correlations indicate that the capability to control vasoconstrictors to the skin is one of the determinant factors maintaining core temperature in human thermoregulatory function. In conclusion, human thermoregulatory function is largely dependent on the suppression and activation capability of vasoconstrictors.

Decoding rule from vasoconstrictor skin sympathetic nerve activity to nonglabrous skin blood flow in humans at normothermic rest.

Although an importance of vasoconstrictor skin sympathetic nerve activity (SNA) in control of cutaneous circulation is widely recognized, the decoding rule that translate dynamic fluctuations of vasoconstrictor skin SNA into skin blood flow is not fully understood. In 10 male subjects who rested in supine position under normothermic condition, we measured skin blood flow index (by laser-Doppler flowmetry) at the dorsum pedis, and vasoconstrictor skin SNA (by microneurography) that was confirmed to innervate the same region as the flow index. We determined the transfer and coherence functions from the neural activity input to the flow and quantified the contribution and predictability from the input to output by system engineering technique. The results showed that in frequency-domain analysis, the transfer function from vasoconstrictor skin SNA to skin blood flow had low-pass filter characteristics with 3.6+/-0.1s of pure time delay. The coherence function was approximately 0.5 between 0.01 and 0.1Hz and less above 0.1Hz. In time-domain analysis, the predictability from the SNA to the skin blood flow was approximately 50%. These findings indicate that at normothermic rest, the decoding rule from vasoconstrictor skin SNA to skin blood flow of skin is characterized by low-pass filter with 3-4s of pure time delay, and that the vasoconstrictor skin SNA contributes to a half of fluctuation of skin blood flow in the condition. The incomplete dependence of skin blood flow on vasoconstrictor skin SNA may confirm nonneural mechanisms to control cutaneous circulation even at normothermic rest.