We investigated the involvement of primary sensory nerves in intestinal autoregulatory escape induced by postganglionic nerve stimulation (NS) in anesthetized rats. Anterior mesenteric artery (AMA) blood flow velocity (BF) was measured with a pulsed Doppler flowmeter. Periarterial NS elicited an abrupt fall in BF, which was followed by a recovery in BF toward the basal value, despite sustained NS. This recovery from NS constituted the neurogenic escape phenomenon. Vasoconstrictor responses to NS were abolished by periarterial application of tetrodotoxin. Acute, surgical interruption of proximal periarterial nerves had no effect on BF responses to distal NS, suggesting a peripheral rather than a central nervous mechanism for the escape phenomenon. Escape from NS-induced vasoconstriction was significantly inhibited by prior administration of the selective sensory neurotoxin capsaicin as either subcutaneous injection in neonatal life, acute application to periarterial nerves, or acute injection into the jejunal lumen. In rats pretreated 24 h with reserpine, NS provoked a vasodilator response that was inhibited by intrajejunal capsaicin. Increases in arterial blood pressure (BP) and heart rate observed during NS were blocked by periarterial (but not intrajejunal) application of capsaicin. Transmural electrical field stimulation elicited significantly greater nerve-induced contractions in AMA rings from control rats. Our findings support the hypothesis that postganglionic NS activates both vasoconstrictor sympathetic nerve branches and vasodilator afferent C-fibers. The latter nerves release vasodilator peptides in the periphery during continuous low frequency NS that appear to be essential for autoregulatory escaped in our model.

Acute and chronic treatments with capsaicin were used to evaluate the role of afferent neurons in the regulation of intestinal blood flow. Experiments were performed on anesthetized rats, in which mean intestinal blood flow was determined with a pulsed Doppler flowmeter, mean systemic arterial pressure was determined with a transducer, and intestinal vascular conductance (C) was calculated from these measurements. Acute administration of periarterial capsaicin (0.5 mg) induced biphasic intestinal vascular responses. An early hyperemic response occurred with a maximal increase in blood flow of 31% at 5 min, followed by a decrease in blood flow of 17% at 30 min. Arterial pressure was decreased by the application of capsaicin, initially by 10%. There was an early increase of 49% in conductance, followed by a 15% decrease, compared with control values. When 1 or 4 mg capsaicin was instilled into the lumen of the jejunum there was a response pattern similar to that observed after periarterial application of capsaicin. Intrajejunal capsaicin (4 mg) increased blood flow by 51%, followed by a decrease of 16%. Mean mesenteric artery conductance was increased by 32% initially and subsequently was decreased by 21%, in response to acute intrajejunal administration of capsaicin. Both mean blood flow and conductance were increased (44% and 76%, respectively) in adult rats chronically pretreated with capsaicin (170 mg total dose) when compared with vehicle-treated controls. However, in rats pretreated neonatally with capsaicin (50 mg/kg) and allowed to mature, basal flood flow was lower than in control animals but C was not different from control littermates.(ABSTRACT TRUNCATED AT 250 WORDS)

Reactive hyperemia (RH) is a local, vascular response that occurs following release from mechanical occlusion of an artery, with restoration of intra-arterial pressure. The mechanism of this postocclusion hyperemia in the gut has not been identified, although metabolic, myogenic, and neurogenic mediators of this response have been proposed. The present study was conducted to evaluate a possible modulatory role for sensory innervation of the intestinal vasculature in RH, using acute and chronic treatment with capsaicin applied in different ways. In anesthetized rats, the velocity of flowing blood in the gut was determined continuously with a pulsed Doppler velocimeter, and arterial pressure was determined with a transducer. The increase in calculated intestinal vascular conductance at the height of RH (Ch), the excess volume of blood accumulating during RH, and the duration of the hyperemia were also used to quantify RH after occluding the anterior mesenteric artery for 30, 60, and 120 sec. In the initial control group of rats, the maximal increases in the velocity of flowing blood during RH were 61 +/- 4%, 90 +/- 7%, and 129 +/- 10% of control, conductances were increased to 192 +/- 5%, 222 +/- 12%, and 267 +/- 15% of control, volumes were 3.5 +/- 0.6 ml, 7.2 +/- 0.4 ml, and 16.2 +/- 1.8 ml, and durations of hyperemia were 78 +/- 5 sec, 93 +/- 6 sec, and 178 +/- 7 sec, respectively, after each elapsed period of occlusion. Acute treatment with periarterial capsaicin significantly decreased peak conductances in RH by 15-35% for all occlusions tested and reduced both volume and duration values. Rats treated with capsaicin in neonatal life exhibited reduced Ch values, as did adult rats treated chronically with capsaicin. Both periarterial and intrajejunal treatment with capsaicin decreased the duration of RH. Hexamethonium increased both Ch and the duration of RH and tended to reverse reductions in these parameters caused by capsaicin. These results suggest that sensory innervation of the intestinal vasculature exerts a modulatory influence in the regulation of intestinal RH.

We evaluated the effects of potential factors in autoregulatory escape from norepinephrine-induced vasoconstriction in rat anterior mesenteric artery. We determined mesenteric artery blood flow velocity with a pulsed Doppler, sonic flowmeter, and systemic arterial blood pressure with a transducer. A 4-min norepinephrine infusion (0.125-1.0 x 10(-8) M/min) intravenously evoked a dose-dependent, initial vasoconstriction that was followed by rapid escape of blood flow toward or above the control value during sustained norepinephrine administration. Neonatal capsaicin treatment enhanced vasoconstrictor responses to norepinephrine but failed to affect escape parameters. Propranolol decreased norepinephrine-induced escape dose dependently. Adenosine deaminase attenuated escape, and the combination of this enzyme plus propranolol nearly abolished escape from norepinephrine-induced vasoconstriction. Methylene blue also diminished autoregulatory escape. These findings suggest that norepinephrine-induced autoregulatory escape involves simultaneous beta-adrenoceptor, purinergic, and endothelial mediation. Norepinephrine-evoked mesenteric vasoconstriction appears to involve predominantly alpha 2-adrenoceptors and is modulated by peptidergic sensory nerves and adenosine.

Cessation of perivascular nerve stimulation (NS) elicits a transient increase in intestinal blood flow above the prestimulatory value. This enhancement of blood flow constitutes the phenomenon of post-nerve stimulation hyperemia (PSH). We investigated the involvement of peptidergic sensory nerves in intestinal PSH. In anesthetized rats the velocity of blood flowing through the anterior mesenteric artery (VBF) was measured with a pulsed Doppler velocimeter. PSH was induced by 4 min of postganglionic electrical NS (5 Hz). PSH was abolished by distal periarterial application of tetrodotoxin and intra-arterial lidocaine, which suggests a peripheral sensory nervous mechanism for PSH. The increase in conductance at peak PSH was blocked by pretreatment with the selective, primary afferent neurotoxin capsaicin administered as 1) subcutaneous injection in neonatal life, 2) topical application to periarterial nerves, or 3) injection into the jejunal lumen. In rats pretreated with reserpine, NS evoked a hyperemic response, which was blocked by capsaicin. Treatment with adenosine deaminase inhibited PSH considerably less than capsaicin, suggesting a lesser role for adenosine in PSH. Our findings support the hypothesis that postganglionic NS activates both adrenergic and peptidergic nerves and that the latter release vasodilator peptides in the gut during PSH.