In the present study, the CPT caused an acute increase in MABP and a transient increase in RBF that corresponded with the increase in blood velocity
(Fig. 1) . After that, vessel diameter began to decrease and the transiently increased RBF returned to baseline. These findings suggest that constriction of retinal arterioles plays an important role in the regulation of RBF in response to an acute increase in systemic BP.
In two previous human studies in which conventional LDV was used, the RBF was maintained until the MABP increased to an average of 115 mm Hg (41% of baseline)
1 or 112 mm Hg (30% of baseline).
5 In the present study, the average peak MABP was 103.7 mm Hg (21.3% of baseline), which is smaller than in the previous studies. Our finding that RBF was finally maintained in response to the increase in MABP is consistent with previously published results. However, the transient increase in RBF observed in our study was not mentioned in the two previous studies. Because it was not technically possible to measure velocity and take photographs simultaneously when using a conventional LDV technique, the dynamic RBF response to the physiologic stimuli could not be precisely evaluated in the previous studies. Our results also indicate that the stabilized LDV system has superior temporal resolution and allows the evaluation of the dynamic change in the retinal circulation.
In the present study, we first showed that there were differences in the latency of the response to the CPT
(Table 2) . Our findings that the peak changes in MABP were observed at 1.5 minutes are consistent with previous findings that the peak responses in MABP occurred in the second minute of the CPT.
17 These findings indicate that activation of the sympathetic neural system is completed at 1 to 2 minutes after the start of the CPT. In addition, the velocity changed along a time course that was roughly parallel to that of the MABP in the present study, which indicates that the change in velocity is dependent on the increase in intravascular pressure when MABP increases during the CPT.
In the present study, the increase in MABP and the peak decrease in diameter were 15.4% (13.2 mm Hg) and 9.3% at T2
(Fig. 1) . The response of retinal arterioles to the increase in MABP was studied previously by Blum et al.,
18 who used the retinal vessel analyzer. They reported that isometric exercise causes a significant increase of 22.8 mm Hg in MABP and a decrease of 5.5% in the diameter of the retinal arterioles. Their results are roughly in agreement with ours in the magnitude of the response to the increase in MABP. These results indicate that constriction of retinal arterioles plays an important role in RBF autoregulation when systemic BP increases.
The details of the mechanisms by which RBF is autoregulated remain to be clarified. Because the CPT is the stimulus for the increase in systemic BP and HR by the activation of the sympathetic nervous system,
19 it is necessary to take into account the neural influence on our data. Although we did not measure the activity of the sympathetic nervous system, the significant increases in the MABP and HR that were observed in the present study
(Fig. 1) indicated the activation of the sympathetic nervous system in response to the CPT in our subjects. Some investigators suggest that the sympathetic nervous system, which affects the peripheral vascular bed to a different extent in many organs, plays some role in regulation of RBF.
20 Conversely, sympathetic nerves are thought to be nonfunctional in the retinal vascular bed.
16 If the constriction of the retinal arterioles originates in the sympathetic neural system, it should have occurred within several seconds and corresponded with the elevation in arterial pressure.
21 Our findings that the peak decrease in diameter was proceeded by the peak changes in MABP and velocity
(Table 2) are consistent with the latter findings. Taken together, it is reasonable to consider that the sympathetic nervous system may not play a major role in the constriction of retinal arterioles that was observed in the present study, in response to the CPT.
The details of the sites at which RBF is autoregulated remain to be clarified.
Figure 2 shows that the peak change in vessel diameter significantly correlated with the peak increase in MABP. Harder
22 found that the pressure elevation in isolated cerebral arteries caused membrane depolarization in vascular smooth muscle, resulting in vessel constriction. His findings indicate that intravascular pressure directly alters the vascular smooth muscle transmembrane potential. Although the exact mechanism responsible for the constriction of the retinal arterioles was not clarified in the present study, our results indicate that the magnitude of the retinal arteriole’s constriction is mainly dependent on the magnitude of the local increase in intravascular pressure. It is therefore reasonable to conclude that the CPT-induced constriction of the retinal arterioles observed in our study is mainly dependent on the increase in intravascular pressure. Moreover, these findings indicate that the RBF may be mainly autoregulated in the retinal arterioles when systemic BP increases.
Myogenic contraction is defined as the contraction of vessels and increase in vascular resistance in response to an increase in pressure. In the present study, it is surprising that the RVR significantly decreased in contrast to the transient increase in RBF at T1 (early phase) and then increased at T2 (late phase;
Fig. 1 ). This opposite change in the RVR is similar to a phenomenon that was observed in cat mesenteric arterioles by Johnson and Intaglietta.
6 They suggest that the autoregulatory myogenic contraction in response to increased arterial BP is necessarily preceded by a brief passive vascular expansion that is expected to produce a transient reduction in resistance. Although we could not observe the dilation of the measured retinal arterioles, the early reduction in RVR observed in the present study may be caused by the passive expansion at any site in the retinal microvasculature in response to an acute increase in MABP and RBF.
Because there were individual differences in the time course of the response to CPT in the present study, it is important to evaluate the dynamic change in each parameter when autoregulation of RBF is examined. Our data showed that the stabilized LVD system enables analysis of the dynamic change in diameter and velocity of the retinal arterioles in response to the acute increase in MABP in the human retinal circulation. It is likely that the timing of the onset, as well as the time course of the hemodynamic change, may identify the nature of vasoregulation.
The present results may be clinically significant. Systemic hypertension may exacerbate some retinal disorders, such as diabetic retinopathy.
2 3 4 In addition, it has been reported that the autoregulation of RBF is impaired in diabetes mellitus.
23 Our finding that the transiently increased RBF returned to baseline when the retinal arterioles constricted
(Fig. 1) suggests that the impaired function of the retinal arterioles causes the failure of the autoregulatory mechanism and increases the pressure in the capillaries, which leads to edema or hemorrhage.
In conclusion, the CPT caused an acute increase in MABP, which was associated with a transient increase in the RBF and blood velocity, followed by constriction of the retinal arterioles and return of the RBF to baseline. Our results suggest that constriction of the retinal arteriole plays an important role in the maintenance of RBF in response to an acute increase in systemic BP.