The effects of the intra-arterial infusion of ATP, ADP and AMP into the internal maxillary artery (IMA), which provides the blood supply to the nasal and forehead regions of the dog, were analyzed. Total blood flow and perfusion pressure measurements in the IMA after administration of each adenyl compound indicated dose-dependent and active vasodilatory responses that were restricted to the ipsilateral vessels. The rank order of potency was ADP ≧ ATP > AMP. In order to determine the microcirculatory effects caused by ADP, the tracer microsphere technique combined with absolute blood flow measurement was used. Intra-arterial infusion of ADP in the range 1-200 nmol/min produced elevations in the IMA flow on the stimulated side that ranged between 11 and 74%. The responses to low doses of ADP were mainly confined to the capillaries (CAP), whereas the arteriovenous anastomoses too were sensitive to high doses. The relative contributions of the anatomically and functionally different compartments of the forehead and nose to ADP-produced relaxations of the CAP were dependent upon their location. The CAP flows in the tissues which play a crucial role in conditioning the inspired air increased significantly, while the compartments of the furred surfaces were less sensitive to ADP. The results suggest that, since ATP, ADP and AMP are effective vasodilatory agents in all the regions examined, purines could have a regulatory or modulatory role in the complex vascular regulation of the nasal and forehead regions.

Bilateral temporoparietal hypoperfusion is a characteristic single photon emission computed tomography (SPECT) finding in Alzheimer's disease (AD). Lactate is a metabolic vasodilator and is known to provoke increased cerebral blood flow (CBF) in healthy adults. This work investigated whether lactate, which is present in high concentrations in AD cerebrospinal fluid, affects AD-specific perfusion abnormalities. Twenty mild-to-moderately demented AD probands participated in the self-controlled study. The regional CBF was examined utilizing (99m)Tc-HMPAO SPECT after sodium lactate infusion (0.5 M, 5 mL/kg body weight) and 0.9% NaCl infusion, one on each of two separate days. Despite the vasodilatator effects of sodium lactate, AD rCBF patterns did not show increase in temporo-parietal regions after its infusion. AD-specific bi-temporo-parietal reduction in CBF was accompanied by further hypoperfusion in the parieto-occipital areas after the sodium lactate infusion in seven patients, while no CBF changes were observed in the case of the remaining 13 probands. The pattern of the CBF abnormalities was not correlated with the apolipoprotein E genotype. The decreased vascular responsiveness to sodium lactate reflects disturbed vasoregulatory processes in AD and it is unlikely that lactate would have any relevance in the treatment of AD-related cerebral hypoperfusion, but could be used to improve the value of perfusion SPECT in the diagnosis of AD.

VIP dilates cerebral vessels and is protective against ischemic brain damage, but the mechanisms of these actions have not been investigated in the newborn. VIP and pituitary adenylate cyclase activating polypeptide (PACAP) are structurally related neurotransmitters potentially acting on common receptors. We tested if 1) VIP‐induced cerebral vasodilation is mediated by a) cyclooxygenase (COX), b) nitric oxide synthase (NOS) or c) PACAP‐receptors; 2) VIP preserves cerebrovascular responsiveness after I/R. Pial arteriolar diameter was measured by intravital microscopy in newborn piglets equipped with closed cranial windows. VIP (10−9−10−6M) caused a significant, dose‐dependent pial arteriolar dilation that was blocked by the non‐selective COX‐inhibitor, indomethacin, only at 10−9−10−8M VIP, was unaffected by the NOS inhibitor, L‐NAME, and reduced by the PACAP antagonists, PACAP 6–27 and 6–38. VIP (10−9M, 20 min before I/R) preserved the endothelium‐dependent response to hypercapnia, but not the neuronal‐dependent reactivity to NMDA. We conclude that 1) vasodilator effect of VIP partially involves COX and common receptors with PACAP and 2) VIP protects cerebrovascular endothelial function against I/R. Supported by the Hungarian Scientific Research Fund (OTKA K63401 and K68976) and the Hungarian Health Science Board (ETT 194042006).

No abstract

IR impairs cerebrovascular reactions to several stimuli in Zucker obese (ZO) rats. However, cerebral artery responses after SAH have not been described in IR. Hemolyzed blood (300μl) or saline was infused (10μl/min) into the cisterna magna of 11–13 week‐old ZO (n=15) and lean (ZL) rats (n=15). One day later, dilator responses of the basilar artery (BA) and its side branch (SB) to acetylcholine (ACh)(10−6M), cromakalim (10−7M, 10−6M) and sodium nitroprusside (SNP)(10−7M) were recorded with intravital videomicroscopy. Saline injected ZO animals showed reduced dilation to ACh (BA=7±4% vs. 21±5%; SB=20±5% vs. 37±8%) compared to ZL rats. Blood injection blunted the response to ACh in both the ZO (BA=4±3%; SB=11±3%) and ZL rats (BA=7±2%; SB=16±4%). Cromakalim (10−6M)‐induced dilation was significantly reduced both in the blood injected ZO animals compared to the saline control (BA=11±3% vs. 27±5%; SB=23±7% vs. 43±11%), and in the blood injected ZL rats vs. its saline control (BA=24±4% vs. 29±3%; SB=39±3% vs. 58±9%). No difference in SNP reactivity was observed. In summary, cerebrovascular reactivity to both endothelium‐ and smooth muscle‐dependent stimuli is severely compromised by SAH in IR animals.