THE EFFECTS OF FOREBRAIN MULTIPLE LESIONS ON THE PRESSOR-RESPONSE INDUCED BY BILATERAL CAROTID OCCLUSION IN CONSCIOUS RATS

In the present study, the effects of electrolytic lesions of the anteroventral third ventricle (AV3V) region and of the medial forebrain bundle (MFB) on the pressor response induced by bilateral carotid occlusion (BCO) in conscious intact and aortic baroreceptor-denervated (AD) rats were investigated. In intact control rats, BCO during 60 s produced a pressor response that could be divided into an early response (ER = 50 +/- 3 mmHg) that reachs a peak during the first 20 s and a sustained late response (LR), smaller than ER (32 +/- 2 mmHg), observed during the last 30 s. In intact-innervated rats, AV3V lesion (2 days) reduced ER (22 +/- 3 mmHg) and LR (16 +/- 2 mmHg), whereas the bilateral MFB lesions (6 days) mainly reduced LR (9 +/- 1 mmHg). Rats with simultaneous lesion of both the AV3V region and the MFB showed additional reduction of the ER (15 +/- 3 mmHg), but not LR (11 +/- 1 mmHg) when compared to the effect of MFB lesions alone. Compared to the AV3V lesion alone, LR but not ER was reduced in rats with a double lesion. In sham-lesioned rats, AD induced a significant increase in the pressor response to BCO (ER = 75 +/- 4 mmHg and LR = 65 +/- 3 mmHg) when compared to intact controls. A similar reduction in ER and LR was observed in AD rats after AV3V (ER = 35 +/- 3 mmHg and LR = 40 +/- 2 mmHg) and MFB (ER = 49 +/- 6 mmHg and LR = 41 +/- 5 mmHg) lesions alone or combined (ER = 40 +/- 6 mmHg and LR = 35 +/- 7 mmHg). The results showed that simultaneous lesions of both the AV3V region and the MFB practically abolished the pressor response to BCO. They also suggested that aortic baroreceptor activity plays a significant role in the effects of AV3V and MFB lesions on the pressor response to BCO.

Granulocyte colony-stimulating factor expression from transduced vascular smooth muscle cells provides sustained neutrophil increases in rats

Granulocyte colony-stimulating factor (G-CSF) regulates granulocyte precursor cell proliferation, neutrophil survival, and activation. Cyclic hematopoiesis, a disease that occurs both in humans and grey collie dogs is characterized by cyclical variations in blood neutrophils. Although the underlying molecular defect is not known, long-term daily administration of recombinant G-CSF eliminates the severe recurrent neutropenia, indicating that expression of G-CSF by gene therapy would be beneficial. As a prelude to preclinical studies in affected collie dogs, we monitored hematopoiesis in rats receiving vascular smooth muscle cells transduced to express G-CSF. Cells transduced with LrGSN, a retrovirus expressing rat G-CSF, were implanted in the carotid artery and control animals received cells transduced with LASN, a retrovirus expressing human adenosine deaminase (ADA). Test animals showed significant increases in neutrophil counts for at least 7 weeks, with mean values of 3,670 +/- 740 cells/mu l in comparison to 1,870 +/- 460 cells/mu l in controls (p < 0.001). Thus, in rats G-CSF gene transfer targeted at vascular smooth muscle cells initiated sustained production of 1,800 neutrophils/mu l, a cell number that would provide clinical benefit to patients. Lymphocytes, red cells and platelets were not different between control and test animals (p > 0.05). These studies indicate that retrovirally transduced vascular smooth muscle cells can provide sustained clinically useful levels of neutrophils in vivo.

Vascular organization of the hystricomorph placenta: a comparative study in the Agouti, capybara, guinea pig, paca and rock cavy

The placental vasculature of five hystricomorph rodents was examined by latex injection of the blood vessels, immunohistochemistry and scanning electron microscopy of vessel casts. The pattern of branching of the vessels is described at the level of fine structure. The placenta is divided into lobes separated by interlobular trophoblast. Fetal arteries course through the interlobular areas and give rise to capillaries from which blood drains into veins at the centre of the lobes. Maternal blood reaches the placenta through spiral arteries that pass around the perimeter of the subplacenta. They supply large maternal blood sinuses, lined by trophoblast, which run through the interlobular areas and into the centre of the lobes. Here they supply fine channels that run parallel to the fetal capillaries, so that maternal blood flows from the centre of the lobe to the periphery. This arrangement provides the morphological basis for countercurrent exchange. The maternal channels of the labyrinth drain into spaces formed by the latticework of the interlobular trophoblast and thence through venous lacunae to a basal venous lacunar ring. The subplacenta is supplied by a single fetal artery. The vessels within the subplacenta pursue a tortuous course with dilatations and constrictions as in an endocrine gland. (C) 2003 Elsevier Ltd. All rights reserved.