RESUMO
The objective of this study was to determine the contribution of renal nerves to the enhanced afferent arteriolar reactivity observed in angiotensin II (Ang II)-induced hypertension. Uninephrectomized Sprague-Dawley rats were divided into four groups: sham rats, renal-denervated rats, Ang II-infused (at 40 ng/min for 13 days) rats, and Ang II-infused+renal-denervated rats. With the use of an implanted arterial catheter, mean arterial pressure (MAP) was monitored in conscious rats. Ang II infusion resulted in a progressive increase in MAP from 98 +/- 1 (day 0) to 166 +/- 7 mm Hg (day 13). This increase in MAP was attenuated in denervated rats and averaged 136 +/- 3 mm Hg on day 13. Kidneys were harvested on day 13 for microcirculatory experiments or measurement of intrarenal Ang II levels. Basal afferent arteriolar diameter was similar in all groups, and group averages ranged from 19.6 to 20.7 microns. Chronic Ang II infusion increased intrarenal Ang II levels. Renal denervation did not alter this effect. Increasing perfusion pressure from 100 to 160 mm Hg reduced afferent arteriolar diameter significantly by 11.2 +/- 0.6% in the sham group and by a similar degree in the remaining three groups. Superfusion with Ang II (10 nmol/L) reduced afferent arteriolar diameter by 34.3 +/- 2.0% in the sham group. This response was enhanced in Ang II-infused (62.3 +/- 3.4%) but not in renal-denervated or Ang II-infused+renal-denervated rats. Additionally, the enhanced afferent arteriolar reactivity to Ang II was not influenced by adrenergic receptor blockade. The afferent arteriolar response to norepinephrine was enhanced in renal-denervated, Ang II-infused, and Ang II-infused+renal-denervated rats compared with sham controls. Administration of the calcium ionophore A23187 decreased afferent arteriolar diameter similarly in all four groups. These results indicate that renal nerves contribute to the development of hypertension and to the enhanced afferent arteriolar responsiveness to Ang II elicited by chronic Ang II infusion.
Assuntos
Angiotensina II/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/fisiopatologia , Rim/irrigação sanguínea , Rim/inervação , Norepinefrina/farmacologia , Sistema Nervoso Simpático/fisiologia , Vasoconstritores/farmacologia , Angiotensina II/metabolismo , Animais , Arteríolas/efeitos dos fármacos , Arteríolas/inervação , Pressão Sanguínea/fisiologia , Calcimicina/farmacologia , Denervação , Hipertensão/induzido quimicamente , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Norepinefrina/metabolismo , Ratos , Ratos Sprague-Dawley , Vasoconstritores/metabolismoRESUMO
Ketorolac is a nonsteroidal anti-inflammatory drug (NSAID) that is indicated for the short-term management of moderately severe, acute pain, that causes analgesia equivalent to that caused by morphine. It has been shown experimentally that the analgesia produced by ketorolac in mice can be diminished by pretreatment with naloxone. This observation suggests that ketorolac produces some of its analgesia by interacting with opioid receptors. However, ketorolac does not directly interact with opioid receptors (Lopez et al., 1987). The present experiments demonstrate that the analgesia produced by ketorolac may be caused by the release of the endogenous opioid, methionine-enkephalin.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Encefalina Metionina/metabolismo , Tolmetino/análogos & derivados , Animais , Encefalina Metionina/sangue , Cetorolaco , Masculino , Radioimunoensaio , Ratos , Ratos Wistar , Tolmetino/farmacologiaRESUMO
The drug Ecstasy (3,4-methylenedioxymethamphetamine (MDMA)) is one of several hallucinogenic amphetamine derivatives reported to be serotonergic neurotoxins. The following is a description of a new high-pressure liquid chromatographic (HPLC) analytical method for the analysis of MDMA, 3,4-methylenedioxyamphetamine (MDA) and N-ethyl-3,4-methylenedioxyamphetamine (MDE) from whole blood. Upon separation of MDMA, MDA and MDE by HPLC, quantitation is achieved by use of electrochemical detection. Retention times for MDA, MDMA, and MDE are 6.5, 9.2, and 10.3 min, respectively, allowing for a complete chromatographic run every 15 min. The sensitivity of the method is 1 ng/ml which allows for measurement of MDA, MDMA, or MDE in microsamples of whole blood. The volume of blood required is very small (200 microliters); therefore, there is minimal blood loss in repeated blood sampling from small animals. Assay linearity was demonstrated from 1 ng/ml to at least 1 microgram/ml. The coefficients of variation for both intra-assay and inter-assay comparisons were less than 9%. Other HPLC methods have been previously described for the analysis of amphetamine derivatives, but this new method offers greater sensitivity, rapid turn-around time and ease of use.
Assuntos
3,4-Metilenodioxianfetamina/análogos & derivados , 3,4-Metilenodioxianfetamina/sangue , Cromatografia Líquida de Alta Pressão , Eletroquímica , 3,4-Metilenodioxianfetamina/metabolismo , Animais , Drogas Desenhadas , Estudos de Avaliação como Assunto , N-Metil-3,4-MetilenodioxianfetaminaRESUMO
Radio-frequency and anodal electrolytic lesions of the paraventricular nucleus (PVN) were found to produce equal and dramatic increases in body weight in female rats. Neither of the groups with lesions had significantly elevated plasma insulin levels during a period of food restriction, but individual values varied greatly. Both groups displayed marked basal hyperinsulinemia after 30 days of food ad lib. It is concluded that radio-frequency and electrolytic PVN lesions produce similar obesity syndromes.
Assuntos
Núcleo Hipotalâmico Paraventricular/fisiologia , Projetos de Pesquisa , Aumento de Peso/fisiologia , Animais , Glicemia/análise , Feminino , Insulina/sangue , Núcleo Hipotalâmico Paraventricular/patologia , Distribuição Aleatória , RatosRESUMO
Female rats were subjected to radio-frequency or anodal electrolytic lesions of the ventromedial hypothalamus (VMH) when 28 days old. Blood samples for determination of basal plasma insulin and glucose levels were taken on postoperative day 30 (Experiment 1) and on day 10 (Experiment 2). Body weight and daily food intake of rats with either type of lesion did not differ from unoperated animals during the first 10 days, but rats with electrolytic lesions, unlike radio-frequency lesioned animals, displayed excess food intake and weight gain starting in the third postoperative week. Both types of lesions produced stunted linear growth and a higher than normal Lee Obesity Index. Only the rats with electrolytic VMH lesions were significantly hyperinsulinemic on postoperative day 30, with a mean plasma insulin level that was at least double that observed in unoperated or radio-frequency lesioned animals. On day 10, however, the animals with electrolytic lesions had markedly lower plasma insulin and glucose levels compared to the other two groups, which did not differ from one another. There was no apparent difference in the size of the lesions produced by the two techniques, and it is therefore concluded that some of the endocrine dysfunctions resulting from electrolytic VMH lesions are due to metallic ion deposits (stimulating adjacent tissue) rather than to tissue ablation.