Enhanced vasoconstrictor responses in renal and femoral arteries of the golden hamster during hibernation.

1. The present study assessed local regulation of vascular tone of euthermic (control), cold control and hibernating golden hamsters. Sympathetic neurotransmission in the renal artery, the long term effects of hibernation on perivascular nerve activity, and the responsiveness of femoral artery to a number of neurotransmitters and hormones with both constrictor and dilator actions during hibernation are described. 2. The contractile responses of the renal arterial rings to transmural nerve stimulation (80 V, 0.1 ms, 4-64 Hz, for 1 s) were negligible in controls, significantly increased at higher frequencies of stimulation in cold controls and markedly enhanced in the hibernating group at all frequencies tested. The contractile responses to exogenous noradrenaline (NA; 0.1-100 microM) were significantly increased in the renal arteries of hibernating hamsters compared with controls, but not compared with cold controls. Responses to exogenous ATP (1-3000 microM) and KCl (120 mM) were similar among all experimental groups. 3. The maximal contractile responses of femoral arterial rings to the sympathetic co-transmitter ATP and 5-hydroxytryptamine were increased by approximately 124% and 99%, respectively, in hibernating compared with cold control preparations without a change in the concentration of agonist that produces half-maximal response. However, the responses to NA were not altered during hibernation. 4. Vasoconstriction of femoral arterial rings in response to arginine vasopressin was significantly enhanced in both cold controls and hibernating groups, while vasoconstriction in response to endothelin-1 and KCl was unaltered. 5. The dilator responses of femoral arterial rings to acetylcholine, sodium nitroprusside and adenosine were not different among the groups. 6. It is suggested that the marked augmentation of sympathetic neurotransmission, selective supersensitivity of the vascular smooth muscle to sympathetic contractile agents and unaltered vasodilatory mechanisms may provide a means for maintenance of vascular tone and peripheral resistance during hibernation.

P2X purinoceptors in postmortem human cerebral arteries.

Pharmacological studies have demonstrated that various purinoceptors are involved in the control of the cerebral vascular tone in many species. In this study, the existence of P2X purinoceptors in the postmortem human cerebral arteries was investigated with organ-bath pharmacology, autoradiography, and immunohistochemistry. Specimens were obtained from the M2 region of the middle cerebral arteries from human cadavers with an age range of 53-91 years and postmortem time of 37-54 h. Application of alpha,beta-methylene adenosine triphosphate (ATP) produced concentration-dependent contraction in the arterial ring, whereas transmural nerve stimulation and noradrenaline did not elicit contraction. Autoradiography using [3H]alpha,beta-methylene ATP (a radioligand for P2X purinoceptors) showed specific [3H]alpha,beta-methylene ATP binding sites in the smooth-muscle cells of the postmortem human cerebral arteries. Immunohistochemistry with specific P2X1 purinoceptor antibodies revealed positive staining exclusively in the smooth muscle of the same specimens. All these results demonstrate the existence of P2X purinoceptors in human cerebral arteries, which were still functionally active despite the long postmortem time. The results from this study suggest that the postmortem human cerebral arteries can be useful specimens for studying the P2X purinoceptor-mediated responses.

Reduced sympathetic noradrenergic neurotransmission in the tail artery of Donryu rats fed with high cholesterol-supplemented diet.

1. Sympathetic neurotransmission and noradrenaline content of the tail artery of Donryu rats fed for 2 months with a cholesterol-supplemented diet enriched with 4% cholesterol, 1% cholic acid, 0.5% thiouracil (CCT), were examined. 2. Total serum cholesterol level of CCT fed rats (7.05 +/- 1.77 mg ml(-1), n = 8) was significantly greater than lab-chow fed controls (2.58 +/- 0.32 mg ml(-1), n = 8). Low density lipoprotein level was also significantly increased in CCT-fed (1.79 +/- 0.26 mg ml(-1), n = 8) compared with control fed rats (1.35 +/- 0.25 mg ml(-1), n = 8) but plasma levels of triglyceride and high density lipoproteins did not differ significantly between the two groups. 3. Contractile responses of the arterial rings to transmural nerve stimulation (65 V, 0.1 ms, 4-64 Hz, 1 s), were markedly attenuated in the CCT fed animals compared with the controls. This reduction involved the noradrenergic rather than purinergic component of sympathetic transmission. 4. Vasoconstrictor responses to exogenous noradrenaline (0.01-300 microM) and adenosine 5'-triphosphate (0.3-1000 microM) were unaffected by CCT diet, indicating prejunctional alteration of sympathetic neurotransmission during CCT-induced hyperlipidaemia. 5. The noradrenaline content of the tail arteries of CCT fed animals (2.64 +/- 0.36 ng mg(-1), n = 6) was significantly lower than that of controls (3.82 +/- 0.32 ng mg(-1), n = 6). 6. These findings show that chronic treatment of Donryu rats with a cholesterol-supplemented diet led to altered levels of circulating lipid fractions accompanied by attenuated sympathetic noradrenergic neurotransmission and reduced noradrenaline content of the rat tail artery.

Enhanced sympathetic neurotransmission in the tail artery of 1,3-dipropyl-8-sulphophenylxanthine (DPSPX)-treated rats.

1. Sympathetic neurotransmission and noradrenaline content of the tail artery of Wistar rats treated for 7 days with the adenosine antagonist, 1,3-dipropyl-8-sulphophenylxanthine (DPSPX), were examined. 2. Systolic blood pressure of the DPSPX-treated rats (164.0 +/- 2.9 mmHg; n = 6) was significantly greater than saline-treated controls (140.0 +/- 2.8 mmHg; n = 5) after 7 days treatment. 3. The pressor responses of the arterial rings to transmural nerve stimulation (65 V, 0.1 ms, 4-64 Hz, for 1 s) were markedly enhanced in the DPSPX-treated compared with the saline-treated animals. Both noradrenergic and purinergic components of perivascular sympathetic neurotransmission were enhanced during DPSPX-induced hypertension. 4. Vasoconstrictor responses to exogenous noradrenaline (0.1-300 microM) and adenosine 5'-triphosphate (0.01-3 mM) were unaffected after DPSPX treatment, indicating prejunctional alteration of sympathetic cotransmission during DPSPX-induced hypertension. 5. Acute exposure to DPSPX (10 microM) did not modify vasoconstrictor responses to transmural nerve stimulation, thus supporting the claim that the enhancement of sympathetic neurotransmission only results from long-term DPSPX treatment. 6. The noradrenaline content of the tail arteries of DPSPX-treated (4.498 +/- 0.26 ng cm-1; n = 4) was significantly greater than saline-treated (3.440 +/- 0.30 ng cm-1; n = 5) animals. 7. These findings show that chronic inhibition of the actions of endogenous adenosine by DPSPX results in an elevation of systolic blood pressure accompanied by enhanced sympathetic cotransmission and enhanced noradrenaline content of the rat tail artery.

Long-term sensory denervation by neonatal capsaicin treatment augments sympathetic neurotransmission in rat mesenteric arteries by increasing levels of norepinephrine and selectively enhancing postjunctional actions.

The present study assessed the long-term effects of sensory denervation on sympathetic innervation in rat mesenteric arteries. Mesenteric arterial beds were isolated from adult rats treated as neonates with capsaicin and from vehicle-treated and untreated rats and perfused at a constant flow rate of 5 ml/min. Frequency-dependent constrictions to electrical field stimulation of sympathetic nerves were markedly augmented in capsaicin-treated rats; maximal constriction was approximately 105% and 169% greater than in vehicle-treated and control preparations, respectively. Maximal contractile responses to norepinephrine (NE) and serotonin (5-HT) were increased by approximately 57% and 85%, respectively, compared with vehicle-treated preparations without a change in the pD2 values. Vasoconstrictions to ATP, vasopressin and KCl were unchanged. In contrast, acute denervation of sensory-motor nerves by in vitro capsaicin treatment had no significant effect on vasoconstrictor responses to electrical field stimulation or to NE, ATP, vasopressin and KCl, although the pD2 value for 5-HT was slightly increased. High-performance liquid chromatographic analysis with electrochemical detection showed an approximately 100% increase in mesenteric arterial NE content after long-term capsaicin treatment. Tissue neuropeptide Y, as assessed by enzyme-linked immunosorbent analysis, was unchanged. In conclusion, long-term sensory denervation of rats produces trophic changes in mesenteric arteries as evidenced by augmented sympathetic vasoconstriction mediated both prejunctionally (increase in tissue NE) and postjunctionally (enhanced responses to NE and 5-HT).

Chronic ethanol consumption affects cholinoceptor- and purinoceptor-mediated contractions of the isolated rat bladder.

Isolated bladder strips from 12-week ethanol-fed, pair-fed and control adult male rats were investigated. Contractile responses to carbachol (CCh; 0.1-300 microM) were statistically significantly potentiated in the ethanol-fed group compared to pair-fed and control. Contractions to beta,gamma-methylene ATP (beta,gamma-MeATP; 1-300 microM) were statistically significantly potentiated in the ethanol-fed group at the highest concentration tested (300 microM). Neurogenic contractions (0.5-32 pps) from the ethanol-fed group in the absence of atropine and after desensitisation by alpha,beta-methylene ATP (alpha,beta-MeATP; 3 microM), were significantly potentiated compared to the pair-fed and control groups; in the presence of atropine (1 microM), neurogenic contractions were significantly augmented at the higher frequencies. It is concluded that chronic ethanol treatment affects both cholinoceptor- and purinoceptor-mediated contractions of the rat bladder.