RESUMO
The sensory nerves, containing substance P and calcitonin gene-related peptide, and noradrenaline-containing sympathetic nerves of the rat uterus were analyzed following long-term sympathectomy with guanethidine in prepubertal (four weeks), young adult (eight weeks) and fully adult animals (18 weeks). Immunohistochemical and histochemical methods were used in association with nerve density measurements and biochemical assays. The main findings were as follows: (1) long-term guanethidine treatment completely abolished the noradrenergic innervation of the uterine horn and parametrial tissue and markedly reduced the tissue levels of noradrenaline in both regions at the three ages analysed; (2) in the uterine horn guanethidine treatment had no effect on the tissue levels of either calcitonin gene-related peptide or substance P or on the density of calcitonin gene-related peptide-containing nerves, at any of the three ages studied; (3) in the parametrial tissue increased levels of calcitonin gene-related peptide were observed at 8 and 18 weeks of age, together with a significant increase in the density of calcitonin gene-related peptide-containing nerves. Substance P levels showed a transient increase in this tissue at eight weeks. In conclusion, long-term sympathectomy with guanethidine resulted in an increase in calcitonin gene-related peptide and substance P in sensory nerves in the parametrial tissue, but not in the uterine horn. The changes in the parametrial tissue only occurred after puberty. It is suggested that sensory nerves in the uterine horn may be less responsive to sympathetic denervation since loss of sympathetic nerves occurs as part of a normal physiological process during pregnancy in this region.
Assuntos
Sistema Nervoso Autônomo/fisiologia , Guanetidina/farmacologia , Plasticidade Neuronal/fisiologia , Neurônios Aferentes/fisiologia , Simpatectomia Química , Útero/inervação , Animais , Sistema Nervoso Autônomo/crescimento & desenvolvimento , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Feminino , Imuno-Histoquímica , Neurônios Aferentes/metabolismo , Neuropeptídeos/metabolismo , Norepinefrina/metabolismo , Ratos , Ratos Wistar , Substância P/metabolismo , Útero/crescimento & desenvolvimento , Útero/metabolismoRESUMO
The plasticity of the sympathetic and sensory innervation of the rat uterus was examined, before and after puberty, in controls and in animals where primary sensory nerves had been destroyed by neonatal capsaicin treatment. Immunohistochemical and histochemical methods were used in association with nerve density measurements and biochemical assays. The main findings were as follows: (1) Puberty was associated with a marked increase in the weight of the uterine horn, uterine cervix and parametrial tissue. This was unaffected by capsaicin treatment. (2) The sympathetic innervation of the uterine horn and parametrial tissue was reduced following puberty as revealed by a decrease in the density of noradrenaline-containing nerves and a marked decrease in the tissue concentration of noradrenaline. Sympathetic nerves supplying the uterine cervix and the blood vessels of the uterus appeared to be unaffected by puberty. (3) In contrast, the sensory supply of the uterus by substance P and calcitonin gene-related peptide-containing nerves increased in parallel with uterine growth during puberty resulting in no change in nerve density and only a slight reduction in peptide concentration. (4) Neonatal capsaicin treatment caused a long-lasting depletion of substance P- and calcitonin gene-related peptide-containing nerves. In the uterine horn and parametrial tissue, capsaicin-resistant calcitonin gene-related peptide, but not substance P, still increased with tissue weight during puberty, indeed, in the uterine horn, the relative increase was greater than in controls. (5) Sensory denervation resulted in an increase in the non-vascular sympathetic supply of the uterus, although there was a regional variation in the time course of the response. Perivascular sympathetic nerves were unaffected by capsaicin treatment. The pattern of change in non-vascular noradrenaline-containing nerves associated with puberty was similar in nature to controls. Thus, there is considerable plasticity in the innervation of the uterus both during puberty and following sensory denervation. A complex pattern of change occurs with differential responses in vascular and nonvascular nerves and in different regions of the uterus. Such differences may be due in part to the different origins of individual nerve populations and/or to their relative sensitivities to sex hormones.
Assuntos
Capsaicina/toxicidade , Neurônios Aferentes/efeitos dos fármacos , Sistema Nervoso Simpático/efeitos dos fármacos , Útero/inervação , Animais , Animais Recém-Nascidos , Vasos Sanguíneos/inervação , Peso Corporal/efeitos dos fármacos , Peptídeo Relacionado com Gene de Calcitonina/análise , Colo do Útero/crescimento & desenvolvimento , Colo do Útero/inervação , Feminino , Fibras Nervosas/efeitos dos fármacos , Plasticidade Neuronal , Norepinefrina/análise , Ratos , Ratos Wistar , Maturidade Sexual , Substância P/análise , Simpatectomia Química , Útero/irrigação sanguínea , Útero/crescimento & desenvolvimentoRESUMO
The postnatal development of noradrenaline (NA)-containing nerves of the rat uterus and its associated blood vessels was investigated using histochemical and biochemical methods. These studies were carried out in conjunction with examination of the morphology of the uterus and the density of blood vessels at the prepubertal, peripubertal and adult stages. It was demonstrated that: (1) the rat uterus is innervated at birth; (2) the innervation of blood vessels develops earlier than that of the myometrium and the density of NA-containing perivascular nerves is not affected by puberty; (3) between birth and day 30 (prepubertal) there was a progressive increase in the innervation of the myometrium which was accompanied by a progressive increase in the total NA content of the organ; (4) at the first oestrus there was a marked increase in the weight of the uterus and isolated myometrial and parametrial tissue. Both muscle cell size and number were also increased. The density of myometrial innervation by NA-containing nerves was markedly reduced, although the total NA content did not change at this stage. This indicates a 'dilution' of myometrial NA-containing nerves in a greater amount of non-neuronal tissue; and (5) between the peripubertal and adult stages there was a further increase in uterine weight together with an increase in the number of smooth muscle cells and a reduction in the density of myometrial NA-containing nerves. Although the density of perivascular nerves was unaffected by puberty, the number of blood vessels supplying the uterus increased during the transition to the adult stage. This was reflected by a significant increase in the total NA content of the uterine horn and of isolated myometrial and parametrial preparations.