Differential distribution of functional alpha(1)-adrenergic receptor subtypes along the rat tail artery

The rat tail artery has been used for the study of vasoconstriction mediated by alpha(1A)-adrenoceptors (ARs). However, rings from proximal segments of the tail artery (within the initial 4 cm, PRTA) were at least 3- fold more sensitive to methoxamine and phenylephrine (n = 6 - 12; p < 0.05) than rings from distal parts (between the sixth and 10th cm, DRTA). Interestingly, the imidazolines N-[ 5-( 4,5- dihydro- 1H- imidazol-2-yl)-2-hydroxy-5,6,7,8- tetrahydronaphthalen- 1- yl] methanesulfonamide hydrobromide (A-61603) and oxymetazoline, which activate selectively alpha(1A)- ARs, were equipotent in PRTA and DRTA (n = 4 - 12), whereas buspirone, which activates selectively alpha(1D)-AR, was approximate to 70-fold more potent in PRTA than in DRTA (n = 8; p < 0.05). The selective alpha(1D)-AR antagonist 8-[2-[4-(methoxyphenyl)-1-piperazinyl] ethyl]-8-azaspiro[4.5] decane-7,9-dione dihydrochloride (BMY- 7378) was approximate to 70- fold more potent against the contractions induced by phenylephrine in PRTA (pK(B) of approximate to 8.45; n = 6) than in DRTA (pK B of approximate to 6.58; n = 6), although the antagonism was complex in PRTA. 5-Methylurapidil, a selective alpha(1A)-antagonist, was equipotent in PRTA and DRTA (pK(B) of approximate to 8.4), but the Schild slope in DRTA was 0.73 +/- 0.05 ( n = 5). The noncompetitive alpha(1B)-antagonist conotoxin rho-TIA reduced the maximal contraction induced by phenylephrine in DRTA, but not in PRTA. These results indicate a predominant role for alpha(1A)-ARs in the contractions of both PRTA and DRTA but with significant coparticipations of alpha(1D)-ARs in PRTA and alpha(1B)-ARs in DRTA. Semiquantitative reverse transcription-polymerase chain reaction revealed that mRNA encoding alpha(1A)- and alpha(1B)-ARs are similarly distributed in PRTA and DRTA, whereas mRNA for alpha(1D)-ARs is twice more abundant in PRTA. Therefore, alpha(1)-ARs subtypes are differentially distributed along the tail artery. It is important to consider the segment from which the tissue preparation is taken to avoid misinterpretations on receptor mechanisms and drug selectivities. antagonism was complex in PRTA. 5- Methylurapidil, a selective alpha(1A)-antagonist, was equipotent in PRTA and DRTA (pK(B) of approximate to 8.4), but the Schild slope in DRTA was 0.73 +/- 0.05 ( n = 5). The noncompetitive alpha(1B)-antagonist conotoxin rho-TIA reduced the maximal contraction induced by phenylephrine in DRTA, but not in PRTA. These results indicate a predominant role for alpha(1A)-ARs in the contractions of both PRTA and DRTA but with significant coparticipations of alpha(1D)-ARs in PRTA and alpha(1B)-ARs in DRTA. Semiquantitative reverse transcription-polymerase chain reaction revealed that mRNA encoding alpha(1A)- and alpha(1B)- ARs are similarly distributed in PRTA and DRTA, whereas mRNA for alpha(1D)-ARs is twice more abundant in PRTA. Therefore, alpha(1)-ARs subtypes are differentially distributed along the tail artery. It is important to consider the segment from which the tissue preparation is taken to avoid misinterpretations on receptor mechanisms and drug selectivities.

RENAL EXCRETION OF ZINC IN NORMAL INDIVIDUALS DURING ZINC TOLERANCE-TEST AND GLUCOSE-TOLERANCE TEST

The urinary excretion, renal clearance, and tubular reabsorption of zinc were investigated in 30 adult healthy subjects under basal conditions and during the zinc and glucose tolerance tests. After a 12h overnight fast, each subject was submitted to renal clearance of zinc. The procedures were performed between 8.00 and 12.00 a.m., after emptying the bladder and ingestion of 4 ml deionized water/kg body weight at 8.00 a.m. The first urine sample was collected at 10.00 a.m., and the second at 12.00 a.m. A dose of 110 mg ZnSO4.7H(2)O was administered orally to each subject, diluted in 20 mi deionized water, at time 0 min. Blood samples were collected from an antecubital vein at times -30, 0, and 30 min and at 30 min intervals up to 240 min. Glucose was administered intravenously (0.5 ml 50%/kg body weight) during the first 3 min of the test, and blood samples were collected from an unconstricted, contralateral, antecubital vein at times -30, 0, 3, 5, 10, 20, 30, 45, 60, and 90 min. The results showed that urinary zinc excretion, and renal zinc clearance were significantly higher during the zinc and glucose tolerance tests than in the control condition. on the other hand, renal zinc clearance was more elevated during the glucose tolerance test than during the zinc tolerance test. Variations in zinc tubular reabsorption and glomerular filtration rate were not detected. The results suggest that urinary excretion and renal clearance of zinc in healthy subjects increase during acute zinc ingestion and glucose infusion. Although zinc ingestion raised urinary zinc excretion, glucose infusion was more effective in increasing renal zinc clearance. These normal parameters are important in the investigation of diabetic patients with serum and urine zinc changes.

Oral health in renal transplant recipients administered cyclosporin A or tacrolimus

OBJECTIVE: the aim of this study was to determine the oral status of renal transplant recipients receiving cyclosporin A (CsA) or tacrolimus (FK-506) as immunosuppressant.SUBJECTS AND METHODS: A total of 88 renal transplant recipients receiving CsA (63 men and 25 women, mean age 51.4 years) and 67 receiving FK-506 (57 men and 10 women, mean age 33.5 years) were included in the study. Donor type, histocompatibility, cold ischemia time and prior delayed graft function were similar between the two groups. Demographics and pharmacological data were recorded for all subjects.RESULTS: the results demonstrated that CsA caused a greater number of oral diseases. A greater number of gingival overgrowth was present in patients treated with CsA. However, the combined use with calcium channel blockers increased the gingival overgrowth number. The occurrence of candida in saliva was observed in 80 renal recipients treated with CsA and 20 treated with FK-506. The presence of squamous oral carcinoma (n = 3) and herpes simplex (n = 10) was observed in patients treated with CsA. These alterations were not observed in renal recipients treated with FK-506.CONCLUSIONS: Renal recipients constitute a high-risk group for oral diseases, as they are immunocompromised. However, the FK-506 regime appears to ameliorate this effect, compared with CsA. Adequate pre- and post-transplant oral health care is recommended for these subjects, irrespective of the time interval for which the drug is administered.

FTY720 prevents renal T-Cell infiltration after ischemia/reperfusion injury

Ischemia/reperfusion (I/R) injury, a common early feature in renal transplantation, results from both free radical species generation and local inflammatory responses that attract different types of cells. The interaction with infiltrating leukocytes could promote damage and death of resident renal cells contributing to worsening of renal function. It has been shown that depletion of host T cells protects against kidney damage after I/R injury, although the mechanism is not fully understood. FTY720, a synthetic analog of a natural product extracted from Isaria sincclairii has shown modulatory properties in experimental models of autoimmune disease, transplantation, and I/R injury. FTY720 alters lymphocyte responses to chemokine homing signals, thereby decreasing the number of lymphocytes in inflammatory sites. We evaluated renal function in mice at 3, 5, and 7 days after I/R injury in the presence or absence of FTY720 treatment. FTY720 treatment promoted earlier recovery of renal function associated with a lower number of renal-infiltrating lymphocytes. These findings confirm previous results showing a protective effect of FTY720 in I/R injury models.

ROLE OF ADRENERGIC PATHWAYS OF THE MEDIAL PREOPTIC AREA IN ANGII-INDUCED WATER-INTAKE AND RENAL EXCRETION IN RATS

In this study, we investigated the participation of adrenergic neurotransmission in angiotensin II- (ANGII)-induced water intake and urinary electrolyte excretion by means of injection of the alpha(1)-, alpha(2)-, and beta-adrenoceptor antagonists and ANGII into the medial preoptic area (MPOA) in rats. Prazosin (an alpha(1)-adrenergic antagonist) antagonized the water ingestion, Na+, K+ and urine excretion induced by ANGII, whereas yohimbine (an alpha(2)-adrenergic antagonist) enhanced the Na+, K+ and urine excretion induced by ANGII. Propranolol (a nonselective beta-adrenoceptor blocker) antagonized the water ingestion and enhanced the Na+ and urine excretion induced by ANGII. Previous treatment with prazosin reduced the presser responses to ANGII, whereas yohimbine had opposite effects. Previous injection of propranolol produced no effects in the presser responses to ANGII. These results suggest that the adrenergic neurotransmission in the MPOA may actively participate in ANGII-induced dipsogenesis, natriuresis, kaliuresis and diuresis in a process that involves alpha(1)-, alpha(2)-, and beta-adrenoceptors.

CHANGES IN VASCULAR-RESISTANCE DURING CAROTID OCCLUSION IN NORMAL AND BARORECEPTOR-DENERVATED RATS

In the present study, we investigated changes in mesenteric, renal, and hindquarter vascular resistance during the pressor response produced by bilateral carotid occlusion (BCO) in conscious, freely moving normal and denervated (aortic, carotid, or both) rats. BCO was performed using special previously implanted cuffs. In control normal rats, the increase in mean arterial pressure (MAP) during early and late responses (37 +/- 4 and 21 +/- 2 mm Hg, respectively) was related to increased renal (125 +/- 12% and 45 +/- 10%) and mesenteric (38 +/- 13% and 41 +/- 5%) but not hindquarter (14 +/- 4% and 8 +/- 7%) vascular resistance. In aortic-denervated rats, the greater MAP increase in early and late responses (57 +/- 4 and 44 +/- 4 mm Hg, respectively) compared with normal rats was related to a marked increase in hindquarter (137 +/- 26% and 106 +/- 26%) and mesenteric (104 +/- 14% and 66 +/- 9%) vascular resistance. In carotid-denervated rats, MAP increase and change in vascular resistance were similar to those values observed in control rats. Sinoaortic-denervated rats showed a greater MAP increase (34 +/- 4 mm Hg) during late response and a reduced increase in renal vascular resistance (46 +/- 6%) during early response. The present results show that 1) the pressor response to BCO in normal rats is associated with an increase in renal and mesenteric vascular resistance, 2) the aortic baroreceptors buffer the increase in mesenteric and especially hindquarter vascular resistance during BCO, and 3) the reduced pressor response in late response is probably related to a reduced increase in renal vascular resistance during this component compared with the early response.