of PPG NOS+ neurons in the elicited increases. Note that 7NI has widely been referred to as a selective nNOS inhibitor. This conclusion was at odds with the published evidence that 7NI is a potent inhibitor of both nNOS and eNOS in vitro, but its isoform selectivity in vivo was hypothesized to be to due to uptake by neurons but not endothelial cells [243]. The evidence for in vivo selectivity was that 7NI reportedly did not produce hypertension. This claim was, however, consistently based on a meager number of animals in the studies claiming selectivity, with the result being that a small hypertensive effect was ignored as insigniÞcant. In our own studies, we showed that 7NI does induce a clear pressor effect in rats when the group size is adequate for statistical power, that this pressor effect is peripherally mediated, and that 7NI does inhibit endothelium-dependent cholinergic vasodilation, all suggesting that the selectivity of 7NI for nNOS over eNOS was overstated [414]. Thus, 7NI is not nNOS selective, as others have now also come to recognize [3, 15].

12.5.3.8 Choroidal Autoregulation and the PPG Input to Choroid – Birds

As part of our interest in the signiÞcance of the facial parasympathetic control of ChBF, we investigated if ChBF in pigeons showed baroregulation (i.e., compensation for perfusion pressure changes caused by BP changes so as to maintain ChBF near basal levels). In one line of study [287], we determined whether pigeons can compensate for an acute decrease in arterial BP and maintain stable ChBF (Fig. 12.18). ChBF was measured using transcleral LDF in anesthetized pigeons, and a stable decrease in arterial BP was produced by blood withdrawal from the brachial artery. The ChBF response to the acute BP drop was assessed by calculating the gain factor (Gf). A Gf of zero means that the ChBF change is completely proportional to the arterial BP change, without compensation (i.e., without baroregulation). A Gf of 1 indicates complete stability of the ChBF despite the change in BP (i.e., perfect baroregulation). During the withdrawal itself, BP decreased rapidly, as did ChBF. The ChBF decline, however, was typically not as great as the

arterial BP decline and showed recovery once arterial BP had stabilized at its lower level. For postwithdrawal BP above 40 mmHg, the Gf by 1 min after blood withdrawal was 0.4Ð0.5, indicating that the decline in ChBF was proportionally less than the decline in arterial BP. When the arterial BP declined to a level at or below 40 mmHg, the Gf was about 0, suggesting that the ChBF could not compensate when arterial BP was this low. While these results were consistent with the dogma that ChBF declines when BP declines, they nonetheless conÞrmed that ChBF does signiÞcantly compensate for BP declines. In a second line of study [287], we determined if ChBF baroregulation occurred during spontaneous BP ßuctuation (Fig. 12.18). We found that ChBF compensated well for arterial BP declines to the 50Ð80 mmHg range and for increases above 130 mmHg (with the Gf approaching 1), but poorly just above and below basal ABP. Additionally, compensation failed below a BP of about 40Ð45 mmHg. Our studies therefore show that signiÞcant ChBF baroregulation does occur in pigeons when the BP deviates +30 or −15 from basal BP. While baroregulation is poor with BP deßections just above and below baseline, these small BP changes exert only a small effect on ChBF, and thus the ChBF stays near baseline notwithstanding the poor baroregulation within this range (Fig. 12.18). Our Þnding that NOS inhibition with LNAME eliminates ChBF baroregulation with blood withdrawal-produced systemic hypotension suggests a possible role of NO-mediated neurogenic mechanisms in the process [287]. The observation that a speciÞc threshold BP change must occur for signiÞcant ChBF baroregulation to be observed is consistent with a neural mechanism, as has been reported to play a role in cerebral blood ßow baroregulation [121, 249]. ChBF baroregulation would prevent under- perfusion-related ischemia or overperfusionrelated edema and impaired ßuid-tissue exchange in the outer retina [35, 162, 170], and thus seemingly be an important ocular homeostatic mechanism. For the cerebral vasculature, in which baroregulation is also evident, both an intrinsic vascular smooth muscle myogenic mechanism (which acts to maintain vessel wall stretch within

bBP-Dependent choroidal blood flow regulation – ChBF changes are smaller than ABP changes

100

90

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Fig. 12.18 In graph (a), the ChBF response to BP ßuctuation was assessed by calculating the gain factor (Gf) as follows, Gf = 1, (dChBF/bChBF)/(dMABP/ bMABP), where dChBF and dMABP are the change in basal (b) ChBF and mean (M) arterial BP after blood withdrawal. A Gf of zero means that the ChBF change is completely proportional to the arterial BP (ABP) change, without compensation (i.e., without baroregulation). A Gf of 1 indicates complete stability of the ChBF despite the change in BP (i.e., perfect baroregulation). For the 25 birds analyzed in a study of the behavior of ChBF during spontaneous ßuctuation in ABP, the mean Gf for ChBF (±SEM) for each 5 mmHg step in ABP was determined and graphed as a function of the corresponding ABP. As can be seen, the Gf values for ChBF were 0.50Ð0.75 (good compensation) over the 50Ð80 mmHg range and

were consistently positive over nearly the entire ABP range examined. Below a BP of 45 mmHg compensation, however, appeared to fail. Graph (b) shows the results for the same 25 birds, with mean ABP for each 5 mmHg step in pressure expressed as a percent of basal ABP. The mean ChBF at each 5 mmHg step was also expressed as a percent of basal ChBF, and each ChBF value (±SEM) was then graphed as a function of the corresponding ABP. The diagonal line indicates the expected ChBF value if ChBF passively changed with declining ABP. As can be seen, ChBF values were consistently higher than would be predicted if ChBF passively followed ABP. ChBF remained near or above 90% of basal over an ABP range of 70Ð100% of basal ABP. Even from 50% to 70% of basal ABP, ChBF showed prominent compensation

a preferred range) and a PPG-mediated neurogenic mechanism have been proposed to contribute to baroregulation to low systemic BP [121, 153, 272]. In addition to a choroidal neurogenic

mechanism, a myogenic regulation has also been proposed to play a role in choroidal baroregulation [169, 170]. Note that ocular perfusion pressure can be modulated by head position due