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A Rubino

Publications and source records attributed to A Rubino.

At least 19 recordsLinked to original sources
PubMed2000

Ischaemic preconditioning of the vasculature: an overlooked phenomenon for protecting the heart?

Exposing the heart to brief episodes of ischaemia protects the myocardium and vascular endothelial cells against functional damage and cell death caused by subsequent prolonged ischaemia. Elucidation of the mechanisms that are involved in this phenomenon known as 'ischaemic preconditioning' and identification of drugs that mimic the protective response have the potential to improve the prognosis of myocardial infarction and other cardiac syndromes dramatically. This article focuses on recent findings on the effects of ischaemic preconditioning of the coronary vasculature, which highlight the endothelium as an important target for a successful therapeutic approach to myocardial ischaemia-reperfusion injury.

Animals↗
PubMed2000

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Journal Article↗
PubMed2000

Enterotoxicity and cytotoxicity of Vibrio parahaemolyticus thermostable direct hemolysin in in vitro systems.

Vibrio parahaemolyticus is a marine bacterium known to be a common cause of seafood gastroenteritis worldwide. The thermostable direct hemolysin (TDH) has been proposed to be a major virulence factor of V. parahaemolyticus. TDH causes intestinal fluid secretion as well as cytotoxicity in a variety of cell types. In this study, we investigated the interplay between the hemolysin's enterotoxic and cytotoxic effects by using both human and rat cell monolayers. As revealed by microspectrofluorimetry, the toxin causes a dose-dependent increase in intracellular free calcium in both Caco-2 and IEC-6 cells. This effect was reversible only when low toxin concentrations were tested. The TDH-activated ion influx pathway is not selective for calcium but admits ions such sodium and manganese as well. Furthermore, in the same range of concentration, the hemolysin triggers a calcium-dependent chloride secretion. At high concentrations, TDH induces a dose-dependent but calcium-independent cell death as assessed by functional, biochemical, and morphological assays.

Animals↗
PubMed1999

Regulation of vascular tone by UTP and UDP in isolated rat intrapulmonary arteries.

Vasoconstrictor and vasodilator responses of isolated rat intrapulmonary arteries to the pyrimidine nucleotides UTP and UDP were evaluated and compared with vascular responses to ATP and its analogues. UTP and UDP (1-500 microM) were equipotent in inducing concentration-dependent vasoconstriction, unaffected by the P2 receptor antagonists suramin (100 microM) and Reactive blue 2 (50 microM); ATP (10-500 microM) produced weaker vasoconstriction. UTP and UDP lacked vasodilator activity, while ATP and its analogue 2-methylthio ATP evoked endothelium-dependent vasodilatation. These results indicate that UTP and UDP evoke vasoconstriction of rat intrapulmonary arteries whereas ATP is predominantly a vasodilator at the same arteries. Furthermore, the pharmacological profile of the native UTP/UDP receptor differs from that of the known P2Y2, P2Y4 and P2Y6 recombinant receptors for pyrimidine nucleotides.

Adenosine Triphosphate↗
PubMed1999

Nitric oxide and endothelin-1 in coronary and pulmonary circulation.

Since the discovery of the vasorelaxant properties of nitric oxide and the vasoconstrictor effect of endothelin-1, there have been many studies of the distribution and functional significance of these agents in various vascular beds. In the coronary and pulmonary circulation nitric oxide and endothelin-1 actions have been largely investigated in terms of an imbalance between the opposing effects of these vasoactive agents leading to pathophysiological conditions. This article review functional and immunocytochemical studies with emphasis on the ultrastructural localization of nitric oxide synthase and endothelin-1 in the coronary and pulmonary vascular beds. Localization of nitric oxide synthase (type III or I or II) has been shown in endothelial cells, smooth muscle, and perivascular nerves of the coronary and pulmonary vascular beds and in the neurons, nerve fibers, and the small granule-containing cells within cardiac ganglia. Endothelin-1 was mainly localized in subpopulations of coronary and pulmonary endothelial cells. These immunocytochemical studies provide information about the sources of nitric oxide and endothelin-1 that contribute to the vasomotor control of cardiac and pulmonary circulation under normal and pathophysiological conditions.

Animals↗
PubMed1999

Increased urinary excretion of collagen crosslinks in type 1 diabetic children in the first 5 years of disease.

To analyze possible early abnormalities in bone resorption in type 1 diabetes mellitus the urinary excretion of the collagen crosslinks pyridinoline and deoxypyridinoline was evaluated by immunoassay in 26 prepubertal diabetic patients (mean age 7.8 +/- 1.6 years, mean duration 3.0 +/- 1.1 years) and 46 healthy children (age 8.3 +/- 1.3 years). Relationships with growth parameters (height-standard deviation score, body mass index and height velocity during the year preceding the study) and metabolic control were sought. Longitudinal and ponderal growth was normal in diabetic children. Urinary collagen crosslink excretion was 88.4 +/- 25 nmol/mmol creatinine (median 86, range 44-146) in diabetic patients and 65.6 +/- 19 nmol/mmol creatinine (median 61, range 32-108) in controls (p = 0. 0002). It was positively influenced by diabetic status (beta = 20.5) and negatively by age (beta = -6.41), controlling by sex and BMI (p = 0.0001). A positive correlation was found between collagen crosslinks and blood glucose (r = 0.48, p = 0.01) or HbA1c levels (r = 0.44, p = 0.02) evaluated at the time of the study, while no significant correlation was found with the mean HbA1c values assessed in the last year or throughout the whole duration of diabetes. Collagen crosslink excretion was significantly increased in patients who presented worsening of their metabolic control in the last 3 months. No relationship was found with the duration of disease or growth parameters. In conclusion, the elevated urinary excretion of collagen crosslinks in diabetic children indicates that bone resorption may be disturbed. Poor metabolic control influences the increased rate of bone resorption and may expose growing diabetic patients to a risk of bone loss.

Blood Glucose↗
PubMed1998

Characterisation of subtypes of the P2X and P2Y families of ATP receptors in the foetal human heart.

ATP exerts a variety of actions within the myocardium, including the regulation of coronary vascular tone and modulation of the autonomic control of the heart. In order to characterise the ATP receptor subtypes involved in these effects, degenerate oligonucleotides were used to clone receptors of both P2X and P2Y families from the human foetal heart. About 1 ng of "Quick-Clone cDNA" from foetal human heart was subjected to amplification with two pairs of degenerate oligonucleotides designed to amplify subtypes of the P2X and P2Y receptor families by means of PCR reactions. The sequence analysis of 34 and 29 clones of the P2X and P2Y receptor families, respectively, demonstrated that P2X1, P2X3 and P2X4 subtypes are present in the human foetal heart together with P2Y6, P2Y2 and P2Y4 receptors. P2X1 and P2Y4 receptor subtypes were here characterised for the first time in the human foetal heart. The present study provides the first molecular characterisation of ATP receptors in the foetal human heart. The results show that many P2 receptor subtypes are expressed in the foetal human heart, perhaps contributing to developmental processes as well as to the activity of the foetal heart.

Amino Acid Sequence↗
PubMed1998

In vivo and in vitro efficacy of octreotide for treatment of enteric cryptosporidiosis.

Previous evidence suggested a role of enterotoxin in the pathophysiology of cryptosporidiosis. If so, antisecretory drugs should be effective in reducing diarrhea. We evaluated the in vivo and in vitro efficacy of octreotide, which possesses antisecretory effects, for cryptosporidial diarrhea. Two children with severe cryptosporidial diarrhea were treated with octreotide. The volume modifications and chemical composition of stools were determined. Fecal supernatant was added to Caco-2 cell monolayers mounted in Ussing chambers with or without serosal octreotide and electrical parameters were monitored. Octreotide was effective in reducing the stool volume and fecal Na+ concentration. Fecal supernatant induced an enterotoxin-like increase in transepithelial potential difference. Octreotide induced a dose-dependent decrease in basal potential difference, consistent with an absorptive effect. In cells pretreated with octreotide, fecal supernatant induced an increase in the potential difference, whose magnitude and duration were significantly reduced compared to untreated cells. These results provide in vivo and in vitro evidence for the secretory nature of cryptosporidial diarrhea and for the efficacy of octreotide through a direct interaction with the enterocyte.

Caco-2 Cells↗
PubMed1997

Immunoreactivity for nitric oxide synthase and endothelin in the coronary and basilar arteries of renal hypertensive rats.

The ultrastructural localization of immunoreactivity to nitric oxide synthase (type-III and type-II) and endothelin-1 was examined by using pre-embedding peroxidase-antiperoxidase techniques in the coronary and cerebral basilar arteries in renal hypertensive rats. Renal hypertension was produced by excision of the right kidney and clipping of the left renal artery. Controls were normotensive sham-operated rats (right surgical nephrectomy; a clip inserted near the left renal artery). Both in controls and hypertensive rats, immunoreactivities for nitric oxide synthase-III and endothelin-1 were localized within subpopulations of endothelial cells. In addition, signs of translocation of nitric oxide synthase-III were noted from the cytoplasm to the Golgi complex in endothelial cells of the basilar artery of hypertensive animals. Neither controls nor hypertensive rats showed immunoreactivity for nitric oxide synthase-II. Preparations of the right coronary artery from hypertensive rats displayed fewer endothelial cells positive to nitric oxide synthase-III than in controls, although there were no significant changes in the distribution of endothelin-1-positive endothelial cells in the coronary artery of hypertensive rats. In contrast, the basilar artery from hypertensive rats displayed no changes in the percentage of endothelial cells immuno-positive either for nitric oxide synthase-III or for endothelin-1. In consequence, the ratio of nitric oxide synthase-III:endothelin-1 was reduced in the coronary but not in the basilar artery. Therefore, the nitric oxide/endothelin-1 system appears to play different roles in the coronary and cerebral circulations during renal hypertension.

Animals↗
PubMed1997

Liver involvement in obese children. Ultrasonography and liver enzyme levels at diagnosis and during follow-up in an Italian population.

Our aim was to evaluate incidence and risk factors of liver involvement in obese Italian children as assessed by both ultrasonographic and biochemical parameters. In seventy-five consecutive obese children (age 9.5 +/- 2.9 years, males/females 41/34), serum levels of enzymes and ultrasonography of the liver were evaluated. Tests were repeated one, three, and six months after starting a moderate hypocaloric diet and an exercise program. Three obese children who were found to have chronic viral hepatitis were excluded from the study. Thirty-eight of 72 (53%) obese children had an ultrasonographic image of bright liver consistent with liver steatosis. The latter was severe in nine children, moderate in 16, and mild in 13. Eighteen obese children (25%) had elevated transaminase levels. Bright liver and hypertransaminasemia were not due to any of the most common causes of liver disease. Both were rapidly responsive to loss of weight, confirming that liver involvement was secondary to obesity and that steatosis or steatohepatitis rather than fibrosis were involved. Obesity duration not more than three years (odds ratio = 4.77), a higher degree of obesity (odds ratio = 2.09), and hypertransaminasemia (odds ratio = 2.15) appeared as important predictive factors of liver involvement at ultrasonography. Incidence of liver involvement assessed by means of ultrasonography is significantly higher than that revealed by measurement of serum liver enzymes. A short duration of obesity emerged as a potentially new risk factor of liver involvement in the pediatric obese population and needs to be confirmed in future studies.

Child↗
PubMed1997

Age-related changes in purinergic and adrenergic components of sympathetic neurotransmission in guinea-pig seminal vesicles.

1. Purinergic and adrenergic components of sympathetic neurotransmission and contractile responses to exogenous alpha,beta-methylene ATP and noradrenaline have been investigated in the seminal vesicles of 1-day (new-born), 2-weeks (young), 12-weeks (adult) and 2-years old (aged) guinea-pigs. 2. In seminal vesicles of new-born guinea-pigs electrical field stimulation (EFS; 80 V, 0.5 ms for 30 s, 2-32 Hz) evoked tonic frequency-related contractions. In 2-weeks old guinea-pigs the tonic contraction masked an initial phasic component of the neurogenic responses, whereas in 12-weeks and 2-years old guinea-pigs, neurogenic responses were biphasic, a phasic response being followed by a tonic contraction. In all experimental groups, prazosin (10(-6) M) blocked the tonic contraction while desensitization of P2X receptors by alpha,beta-methylene ATP (10(-4) M) abolished the phasic responses. 3. The phasic purinergic component of the neurogenic response was significantly higher in 12-weeks and 2-years old animals, compared with 2-weeks old guinea-pigs. At 32 Hz phasic contractions were (mN mg(-1) tissue): 0.047+/-0.012, 0.018+/-0.040 and 0.147+/-0.026 in 2-weeks, 12-weeks and 2-years old guinea-pigs, respectively. In contrast, the tonic adrenergic component of the neurogenic contraction significantly declined at 12-weeks and 2-years compared with 2-weeks old guinea-pigs. 4. Contractile responses (mN mg(-1) tissue) to the highest concentration of alpha,beta-methylene ATP tested were significantly higher in 2-weeks (0.248+/-0.022) than in 1-day old animals (0.113+/-0.012) and decreased in 12-weeks (0.163+/-0.016) and 2-years old guinea-pigs (0.200+/-0.008). The pD2 values for the purinoceptor agonist were also significantly lower in adult (4.74+/-0.20) and aged guinea-pigs (5.22+/-0.08) compared with 2-weeks old animals (5.91+/-0.27). Conversely, responses to the highest concentration of noradrenaline gradually decreased with age, without significant changes in the pD2 values. Contractile responses to KCl (240 mM) did not differ significantly between the experimental groups. 5. These results demonstrate age-related changes in purinergic and adrenergic components of sympathetic neurotransmission in the guinea-pig seminal vesicles. The purinergic component is absent in new-born animals and it appears fully developed in adult and old guinea-pigs, while the adrenergic component decreases with age. Pre- and postjunctional mechanisms contributing to the age-related changes of sympathetic neurotransmission are discussed.

Adenosine Triphosphate↗
PubMed1997

Calcitonin gene-related peptide (CGRP)-evoked inotropism during hyper- and hypo-sensory-motor innervation in rat atria.

1. Positive inotropic responses to calcitonin gene-related peptide (CGRP) were evaluated in atria isolated from in vivo rat models of hyper-sensory-motor innervation (following neonatal guanethidine treatment) and hypo-sensory-motor innervation (following neonatal capsaicin treatment), to explore the hypothesis that functional responsiveness of atrial myocardium to CGRP may correlate with tissue levels of the sensory-motor neurotransmitters. Comparative of inotropic responses to CGRP following in vitro treatment of atria with guanethidine was also performed. 2. Following long-term guanethidine treatment, positive inotropic responses to CGRP were significantly attenuated, while supersensitivity to the sympathetic transmitter noradrenaline was shown. Maximal inotropic responses to CGRP (30 nM) were 214.0 +/- 28.1 (n = 8) and 146.8 +/- 21.7 mg (n = 8; P < 0.01) increase of the basal contractile tension in control and treated preparations, respectively. The pD2 values for noradrenaline were 6.71 +/- 0.12 (n = 8) and 7.26 +/- 0.13 (n = 6; P < 0.01) in control and treated atria, respectively. Acute application of guanethidine in vitro did not modify the positive inotropism by CGRP or the beta-adrenoceptor agonist isoprenaline. 3. Sensory-motor hypoinnervation following chronic treatment with capsaicin did not affect the inotropic responses to CGRP. Neither guanethidine nor capsaicin treatment affected the contractile apparatus of myocytes, as demonstrated by similar basal contractile tension as well as calcium-evoked inotropic responses in control and treated preparations. 4. In summary, increased sensory-motor innervation, following long-term sympathectomy with guanethidine, resulted in attenuation of the inotropic responses of the rat atrium to CGRP, while no changes in the inotropic responses were seen following sensory-motor denervation with capsaicin. Down-regulation of CGRP receptors or altered post-receptor signalling may be involved in the reduced responsiveness to CGRP.

Adrenergic alpha-Agonists↗
PubMed1997

Enteric cryptosporidiosis in pediatric HIV infection.

BACKGROUND: Enteric cryptosporidiosis is a frequent problem in adults with human immunodeficiency virus (HIV) infection, but little is known of its features in children. The aim of this study was to investigate the incidence and the clinical features of cryptosporidiosis in HIV-infected children. METHODS: Thirty-five children with symptomatic HIV infection were screened every 2 months, and in case of diarrhea, for the presence of Cryptosporidium. Intestinal function tests were performed, and the fecal osmotic gap was measured in children with cryptosporidiosis. RESULTS: Seventy episodes of diarrhea occurred in 16 children in a median period of 17 months. Cryptosporidium was detected in five cases, all with full-blown acquired immunodeficiency syndrome. Cryptosporidiosis was significantly more protracted than any other form of diarrhea and was associated with dehydration and severe weight loss. Intestinal function was not modified during cryptosporidiosis. Osmotic gap values were consistent with secretory rather than osmotic diarrhea. In four cases, recovery was observed without specific treatment. CONCLUSIONS: Enteric cryptosporidiosis is a severe problem in advanced stages of HIV infection. It does not induce intestinal malabsorption. It induces diarrhea of secretory type. Recovery may be observed independently of therapy.

Animals↗
PubMed1997

Sympathetic neurotransmission in isolated rat atria after sensory-motor denervation by neonatal treatment with capsaicin.

Long-term interactions between sympathetic and sensory-motor nerves have been shown in several tissues. Previous investigations in this laboratory have demonstrated an increase in cardiac sensory-motor innervation after neonatal sympathectomy by guanethidine and an increase of perivascular sympathetic neurotransmission after neonatal treatment by capsaicin. The present study evaluated the effects of sensory-motor denervation on sympathetic neurotransmission in the heart. Newborn rats were injected with capsaicin or its vehicle (Tween 80). Sympathetic neurotransmission was studied in isolated atria driven at a constant rate (4 Hz) by measuring cardiac responses to electrical field stimulation, in the presence of atropine 1 microM. Inotropism of tyramine, norepinephrine and calcitonin gene-related peptide was also tested. Neonatal capsaicin treatment did not affect cardiac responses to trains of an increasing number (2-32) of field pulses. Moreover, inotropic responses to tyramine did not differ between control, capsaicin- and Tween 80-treated preparations. Neither maximal effect nor pD2 values were significantly different between the groups. Similarly, the inotropism of calcitonin gene-related peptide was comparable in all groups of atrial preparations. In marked contrast to earlier papers on blood vessels, this study shows a lack of effect of sensory-motor denervation by neonatal capsaicin treatment on cardiac sympathetic neurotransmission. The different neuronal plasticity of vascular and cardiac sensory innervation will be discussed. The present results also indicate that capsaicin-induced sensory-motor denervation is not associated with changes in cardiac responsiveness to calcitonin gene-related peptide.

Animals↗
PubMed1996

Possible role of diadenosine polyphosphates as modulators of cardiac sensory-motor neurotransmission in guinea-pigs.

1. Isolated guinea-pig atria were used to study the neuromodulatory effect of diadenosine polyphosphates (APnA) on cardiac capsaicin-sensitive sensory-motor neurotransmission. 2. In the presence of atropine, guanethidine and propranolol, electrical field stimulation (EFS) of the atrial preparations evoked a positive inotropic response which is known to be mediated by release of calcitonin gene-related peptide (CGRP) from sensory-motor nerves. P1,P2-diadenosine pyrophosphate (AP2A), P1,P3-diadenosine triphosphate (AP3A), P1,P4-diadenosine tetraphosphate (AP4A), P1,P5-diadenosine pentaphosphate (AP5A) and P1,P6-diadenosine hexaphosphate (AP6A) inhibited in a concentration-dependent way (0.1-30 microM) cardiac responses to EFS. The inhibitory effect of APnA was mimicked by adenosine. 3. All the APnA tested had a direct negative inotropic effect, by reducing in a concentration-dependent manner the basal contractile tension. The inotropism of APnA was comparable to that of adenosine. 4. Both inhibition of cardiac responses to EFS and negative inotropism of AP2A, AP3A and AP4A were sensitive to the antagonism by the A1 adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 0.1-1 nM). The extent of antagonism of DPCPX for the APnA tested was comparable to that for adenosine. 5. Despite the direct negative inotropism, AP4A tested at the highest concentration used did not affect the cardiac responses to the neurotransmitter CGRP, applied exogenously. 6. These results have demonstrated that in isolated guinea-pig atria APnA inhibited sensory-motor neurotransmission, without affecting cardiac responses to exogenous CGRP. The effect of APnA was sensitive to antagonism by DPCPX, which suggests it operates via the activation of prejunctional A1 adenosine receptors. A postjunctional negative inotropism was also shown, mediated by myocardial A1 adenosine receptors.

Adenine Nucleotides↗
PubMed1996

Evidence for a P2-purinoceptor mediating vasoconstriction by UTP, ATP and related nucleotides in the isolated pulmonary vascular bed of the rat.

1. The vasoconstrictor effects of uridine 5'-triphosphate (UTP), uridine 5'-diphosphate (UDP), uridine 5'-monophosphate (UMP) and uridine were tested in the isolated pulmonary vascular bed of the rat. Comparison was made with the effects of adenine nucleotides, adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP), adenosine 5'-monophosphate (AMP) and with adenosine. The effect of P2x-purinoceptor desensitization and blockade was compared on the vascular responses to uracil and adenine nucleotides. 2. At doses ranging from 10(-8) to 10(-5) mol, UTP elicited dose-dependent vasoconstriction. UDP was equiactive to UTP, while UMP and uridine did not show vasomotor activity. Similarly, ATP showed dose-related vasoconstrictor activity. ADP was less potent than ATP in eliciting vasoconstriction, while AMP was active only at the higher doses tested and adenosine was ineffective. 3. Vasoconstriction was produced by ATP analogues with the following order of potency: alpha, beta-methylene ATP > ATP gamma S > beta, gamma-methylene ATP > 2-methylthio ATP > or = ATP. 4. Desensitization of P2x-purinoceptors by the selective agonist alpha, beta-methylene ATP did not modify the vasoconstrictor activity of UTP and UDP and only partially reduced vasoconstrictor responses to ATP, while it abolished vascular responses to alpha, beta-methylene ATP itself. 5. The antagonists of P2-purinoceptors, suramin and pyridoxalphosphate-6-azophenyl-2', 4'-disulphonic acid (PPADS), did not affect vascular responses to UTP and UDP, but reduced vasoconstriction evoked by beta, gamma-methylene ATP and ATP by about 70 and 30%, respectively. 6. This study demonstrates that uracil nucleotides, UTP and UDP, elicit vasoconstriction in the rat pulmonary vascular bed. In addition to confirming the presence of classical P2x-purinoceptors, these results also suggest the presence of a distinct purinoceptor subtype which mediates UTP- and ATP- evoked vasoconstriction in the rat pulmonary circulation.

Adenosine Triphosphate↗
PubMed1996

Augmented sensory-motor vasodilatation of the rat mesenteric arterial bed after chronic infusion of the P1-purinoceptor antagonist, DPSPX.

1. The effect of long-term antagonism of P1-purinoceptors on vascular function was examined in the perfused mesenteric arterial bed isolated from rats which had received constant infusion of either the non-selective P1-purinoceptor antagonist, 1-3-dipropyl-8-sulphophenylxanthine (DPSPX, 30 micrograms kg-1 h-1, i.p.) or saline for seven days. Sympathetic and sensory-motor neurotransmission, smooth muscle and endothelial function were assessed. 2. Basal tone was similar in mesenteric arterial preparations from control and DPSPX-treated rats. Continuous perfusion with methoxamine (7-70 microM) induced similar increases in tone in control and DPSPX-treated preparations. In the presence of guanethidine (5 microM), electrical field stimulation (EFS; 1-12 Hz, 60V, 0.1 ms, 30 s) elicited frequency-dependent vasodilatation due to activation of sensory-motor nerves. In tissues from DPSPX-treated rats the nerve-mediated vasodilator responses were markedly augmented at all frequencies. Maximal relaxation at 8 Hz was 38.34 +/- 4.76% (n = 5) in controls and 65.92 +/- 3.68% (n = 5) after DPSPX-treatment (P < 0.01). Adenosine (3 microM) inhibited the frequency-dependent sensory-motor neurotransmission similar in preparations from controls and DPSPX-treated rats. 3. In raised-tone preparations calcitonin gene-related peptide (CGRP; 5,15 and 50 pmol), the principal vasodilator transmitter of sensory-motor nerves in rat mesenteric arteries, produced similar relaxations in control and DPSPX-treated preparations. Vasodilator responses to the sensory neurotoxin capsaicin (50 and 500 pmol) were also similar between the groups. 4. Assay of tissue CGRP levels of the superior mesenteric artery by enzyme-linked immunosorbent assay showed no significant difference in tissue levels of CGRP in controls, 120.25 +/- 26.34 pmol g-1 tissue (n = 6) and with DPSPX-treatment, 82.12 +/- 24.42 pmol g-1 tissue (n = 6). 5. In raised-tone preparations dose-dependent endothelium-dependent vasodilatation to acetylcholine and ATP, and endothelium-independent vasodilatation to sodium nitroprusside were similar in control and DPSPX-treated preparations. 6. EFS (4-32 Hz, 90V, 1 ms, 30 s) elicited frequency-dependent vasoconstriction due to activation of sympathetic nerves which was similar in controls and in DPSPX-treated preparations. Adenosine (10 and 30 microM) inhibited sympathetic neurotransmission similarly in control and DPSPX-treated preparations. Dose-dependent vasoconstriction to noradrenaline (NA) and ATP, and to KCI (0.15 mmol) was similar between the groups. 7. High performance liquid chromatographic analysis of tissue NA showed no significant difference in NA content of the superior mesenteric artery from DPSPX-treated (1.38 +/- 0.09 ng mg-1, n = 6) and control rats (1.46 +/- 0.17 ng mg-1, n = 6). 8. In conclusion, in rats with hypertension due to 7 days treatment with the P1-purinoceptor antagonist, DPSPX, there is an increase in sensory-motor vasodilatation of the mesenteric arterial bed. There is no change in sympathetic nerve, endothelial or smooth muscle function. Augmented sensory-motor neurotransmission, which does not involve a change in postjunctional responsiveness to CGRP or in the CGRP content of sensory-motor nerves, could be a compensatory change in response to the DPSPX- induced hypertension.

Adenosine↗