Eliete Bouskela

Inhibition of nitric oxide synthase attenuates the cerebral blood flow response to stimulation of postganglionic parasympathetic nerves in the rat.

Stimulation of cerebrovascular parasympathetic nerves markedly increases cortical blood flow. Nitric oxide (NO) or a NO-containing compound is present in these nerves and may therefore, upon release, be partly responsible for the flow increase. In addition, transmitters released from the nerves may cause synthesis and release of this compound from the endothelium. The contribution of NO synthesis to the cortical blood flow (CoBF) increase during parasympathetic stimulation was elucidated in rat by laser–Doppler flowmetry. Thirty-minute exposure to circulating Nω-nitro-l-arginine methyl ester (l-NAME) 50 mg kg−1 eliminated most of the response (from 104 to 8% increase), whereas 10-min exposure to this dose or 30-min exposure to 5 mg kg−1 caused a less marked reduction. The reducing effect was particularly evident after elimination of the systemic blood pressure increase caused by l-NAME (only 3% increase after the high dose). Infusion of l-arginine restored the flow response. Resting CoBF was not substantially affected by blockade of NO formation. Thus, release of an NO-containing compound constitutes a major component of the increase in CoBF caused by parasympathetic nerve stimulation but does not seem to contribute to cortical flow regulation during resting conditions.

Interaction between cerebrovascular sympathetic, parasympathetic and sensory nerves in blood flow regulation

Morphological and pharmacological findings support that different cerebrovascular nerve types have close relationships in the vessel wall and that interactions may contribute to the control of vascular tone. This study in rat investigates whether interaction in blood flow regulation occurs between sympathetic, parasympathetic and sensory nerves in the cerebral vessels. Cortical blood flow (CBF) was measured with a laser-Doppler flowmeter during electrical stimulation of one of the nerves, with or without prior denervation of one or two of the other nerves. Unilateral sympathetic stimulation significantly decreased CBF ipsilaterally. The response was unaffected in magnitude and time course by parasympathetic or sensory denervation. Sensory nerve stimulation did not significantly affect CBF, even after sympathetic denervation. Parasympathetic nerve stimulation caused a marked increase in CBF, which was similar in magnitude in the presence or absence of sympathetic innervation. However, the return to the basal CBF level after parasympathetic stimulation was prolonged after sympathetic denervation. Thus, activation of the sympathetic nerves may contribute to a rapid normalization of the enhanced CBF during parasympathetic nerve stimulation, whereas the reverse phenomenon, parasympathetic normalization of the sympathetically induced CBF reduction, does not occur.

Influence of cerebrovascular parasympathetic nerves on resting cerebral blood flow, spontaneous vasomotion, autoregulation, hypercapnic vasodilation and sympathetic vasoconstriction

Activation of perivascular parasympathetic nerves enhances cerebral blood flow. In the present experiments, functional aspects of this flow regulating capacity were investigated. It was found that parasympathetic nerve stimulation does not facilitate the normalization of the cerebral blood flow reduced by sympathetic stimulation. In contrast, activation of sympathetic nerves may contribute to a rapid normalization of the cerebral blood flow increased by parasympathetic stimulation. The lower limit of cerebral autoregulation is shifted towards higher blood pressures in parasympathetically denervated rats. Parasympathetic nerves do not influence hypercapnic cerebral vasodilatation, but CO2 influence the effect of parasympathetic stimulation on cerebral blood flow. We conclude that activity in parasympathetic nerves does not contribute to cerebral vasomotion.

Effects of Buflomedil on Spontaneous Vasomotion and Mean Arteriolar Internal Diameter in the Hamster Cheek Pouch

Intravital microscopy of the hamster cheek pouch microvasculature was used for in vivo studies on the effects of buflomedil, phentolamine (alpha-adrenergic receptor antagonist) and norepinephrine on the mean internal arteriolar diameter and spontaneous vasomotion. All drugs were applied topically. The vasomotor activity was studied in 125 arterioles (internal diameter range 18.0-62.0 microns) of 34 preparations. Addition of buflomedil (10(-9) to 10(-5) M) did not affect the arteriolar diameter significantly (from 100.7 +/- 3.5 to 106.4 +/- 1.8%, values expressed in percent of the initial diameter as mean +/- SE), but increased the vasomotion frequency and amplitude by approximately 20% (from 7.5 +/- 0.3 to 9.2 +/- 0.2 cpm) and 30% (from 7.3 +/- 0.3 to 10.0 +/- 0.5 micron), respectively. Phentolamine (10(-9) to 10(-5) M) dose-dependently increased the microvascular diameter (from 102.3 +/- 1.2 to 139.1 +/- 4.3%) and reduced the vasomotion frequency and amplitude (from 8.0 +/- 0.3 to 1.9 +/- 0.5 cpm and from 9.0 +/- 2.1 to 3.1 +/- 0.2 microns, respectively). Addition of buflomedil (10(-7) M) reduced the vasodilation evoked by phentolamine (from 103.3 +/- 0.7 to 127.0 +/- 1.5%) and potentiated its depressive effect on vasomotion frequency and amplitude (from 7.6 +/- 0.1 to 1.0 +/- 0.3 cpm and from 9.0 +/- 0.3 to 1.9 +/- 0.6 microns, respectively). Norepinephrine (10(-9) to 10(-5) M) dose-dependently decreased to arteriolar diameter (from 102.3 +/- 0.7 to 69.6 +/- 1.6%) and the vasomotion frequency and amplitude (from 8.4 +/- 0.2 to 0.4 +/- 0.3 cmp and from 8.7 +/- 0.2 to 0.5 +/- 0.4 microns, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Distensibility of Capillaries in the Bat Wing

Preliminary experiments in our laboratory have shown that the distensibility characteristics of the capillary compartment in the bat wing depended upon its location in the vascular tree. The capillaries were then divided into arteriolar, middle and venular segments (according to their proximity to precapillary sphincters or nonmuscular venules). The bat was enclosed in an airtight box, one wing protruding through a slit and extended over a glass plate for microscopic observations. Continuous recordings of the diameter of the capillary segments were obtained; after 5 min of control recordings, the box pressure was raised in steps of 25 mm Hg to a maximum of 100 mm Hg and then returned to control level. The duration of each step was 4 min. Each increase of the pressure led to the dilatation of the capillary, but its arteriolar segment appeared to be more distensible than the middle and venous ones. After shifting the box pressure, the diameter increase was gradual and capillary distensibility decreased with increasing pressure (the venular segment showed the most prominent reduction in distensibility). These findings suggest the existence of a longitudinal gradient of distensibility in the capillary compartment.

The role of nitric oxide in the cerebrovascular flow response to stimulation of postganglionic parasympathetic nerves in the rat

Stimulation of cerebrovascular parasympathetic nerves markedly increases cortical blood flow. Nitric oxide (NO) or a NO containing compound is present in these nerves, and its release may therefore be partly responsible for the flow increase. In addition, transmitters released from the nerves may cause synthesis and release of this compound from the endothelium. The contribution of NO synthesis to the cortical blood flow increase during parasympathetic stimulation was elucidated in rats by laser-Doppler flowmetry. Thirty min exposure to circulating N omega-nitro-L-arginine methyl ester (L-NAME) 50 mg.kg-1 eliminated most of the response (from 104 to 8% increase), whereas 10 min exposure to this dose or 30 min exposure to 5 mg.kg-1 caused a less marked reduction. The reducing effect was particularly evident after elimination of the systemic blood pressure increase caused by L-NAME (only 3% increase after the high dose). In fusion of L-arginine restored the flow response. Resting cortical blood flow was not substantially affected by blockade of NO formation. Thus, release of a NO containing compound constitutes a major component of the increase in cortical blood flow caused by parasympathetic nerve stimulation, but does not seem to contribute to cortical flow regulation during resting conditions.