A comparison of the effects of angiotensin II and norepinephrine on intrarenal arteries in the rat.
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Biomedical subjects
Publications and source records attributed to S K Wilson.
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Perfusion-fixation and vascular casting were used to determine if angiotensin II and norepinephrine cause constriction of afferent arterioles, and if so, whether or not the constriction is principally attributable to a secondary (autoregulatory) response to elevated pressure in the renal circulation. Rats were divided into six groups, and were given five minute infusions of angiotensin II, norepinephrine, or normal saline before perfusion-fixation. Angiotensin II infusions were given to animals in Groups 1 and 2; in Group 1 the renal circulation was exposed to elevated blood pressure, but in Group 2 intrarenal pressure was maintained at normal levels by partial ligation of the aorta above the renal arteries. Groups 3 and 4 were comparable to Groups 1 and 2 respectively, except that norepinephrine was infused instead of angiotensin II. Groups 5 and 6 received infusions of normal saline instead of vasopressor substances. In Group 5, renal vessels were perfusion-fixed at elevated pressures, while in Group 6 renal vessels were perfusion-fixed at normal pressures. Scanning electron microscopy was used to examine and measure vascular casts of 40 to 50 afferent arterioles from each rat. In Groups 1 through 4, casts of afferent arterioles showed severe, focal, and irregularly distributed constriction. In Groups 5 and 6 there was no qualitative evidence of afferent arteriolar constriction or irregularities in vessel caliber. Vessel diameter measurements were significantly smaller in Groups 1 to 4 when compared to Groups 5 and 6, and arteriolar constriction in the juxtamedullary and cortical regions was quantitatively comparable in Groups 1 to 4. Arteriolar diameters in Group 5 were somewhat, but not significantly smaller than those in Group 6, suggesting that perfusion-fixation at elevated pressure alone may have made a minor contribution to afferent vasoconstriction. However, this constriction was clearly not of the same pattern or magnitude as that produced by angiotensin II or norepinephrine infusions. The results indicate that both angiotensin II and norepinephrine cause severe focal constriction of afferent arterioles, and that this constriction cannot be attributed primarily to a pressure-induced autoregulatory response in the renal vasculature.
A semiquantitative glomerular damage index (GDI) was determined for overall (O), superficial (S), and juxtamedullary (JM) glomeruli in four models of experimental hypertension in the rat to assess the severity and distribution of injury in light of present day knowledge of glomerular hemodynamics. After a four week period of similar hypertension, comparison of Group 1 (renal ablation) with Group 2 (aortic ligature) revealed OGDIs of 0.420 +/- 0.064 (SEM) vs. 0.062 +/- 0.019, P less than 0.0001, SGDIs of 0.250 +/- 0.071 vs. 0.035 +/- 0.007, P less than 0.0089, and JGDIs of 0.455 +/- 0.071 vs. 0.155 +/- 0.036, P less than 0.002. Within Group 1 the SGDI and JMGDI were not significantly different but within Group 2 the SGDI was less (P less than 0.005) than the JMGDI. Arterial/arteriolar damage was comparable in both groups. After an eight week period of similar hypertension, comparison of Group 3 (deoxycorticosterone-saline) with Group 4 (stroke-prone spontaneously hypertensive rats) showed OGDIs of 0.301 +/- 0.065 vs. 0.128 +/- 0.023, P less than 0.025, SGDIs of 0.289 +/- 0.096 vs. 0.072 +/- 0.015, P less than 0.044, and JMGDIs of 0.394 +/- 0.083 vs. 0.307 +/- 0.062, NS. Within Group 3 the SGDI and JMGDI were not significantly different, but within Group 4 the SGDI was less (P less than 0.002) than the JMGDI. Vascular damage in the two groups was comparable. Taking into account known physiologic data, the findings are consistent with the idea that increased preglomerular resistance is protective of glomeruli, whereas decreased resistance with increased pressure and/or flow is injurious.(ABSTRACT TRUNCATED AT 250 WORDS)
The authors compared behavior problems and social competence in 126 boys and girls (age 6-11) from violent and nonviolent families, on the basis of maternal ratings on the Achenbach Child Behavior Checklist. Girls from violent families were reported as showing more internalizing behavior problems and a lower level of social competence than their nonviolent comparison group. Boys from violent families were reported as demonstrating both internalizing and externalizing behavior problems, in addition to having a lower level of social competence. For boys, the level of exposure to violence between parents was significantly associated with greater adjustment problems.
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A perfusion-fixation and vascular casting technique was used to assess the effects of acute, angiotensin-induced hypertension on the intrarenal arteries and, for comparison, the small arteries of the intestine. The first objective was to establish that the technique accurately preserves postmortem the vascular changes induced by acute hypertension. To do this, the easily accessible intestinal arteries were examined and photographed both in vivo and after fixation and injection of Batson's no. 17 casting resin in a group of angiotensin-treated rats and controls. The second objective was to apply the technique to observe and compare acute hypertensive changes in the intrarenal and intestinal arteries; studies included scanning electron microscopy of vascular casts and transmission electron microscopy of vessel walls using ferritin as a tracer to assess permeability. In the angiotensin-treated rats, casts of both intrarenal and intestinal arteries showed many well-defined zones of constriction and nonconstriction. Transmission electron microscopy of both the smaller intrarenal (interlobular) arteries and intestinal vessels revealed focal smooth muscle rarefaction and abnormal permeability to ferritin, found only in the nonconstricted zones. This study provides new evidence that in the kidney, as in the intestine, acute hypertension produces a characteristic pattern of arterial constriction and nonconstriction, and that hypertensive vascular lesions with accompanying increased permeability occur exclusively in the nonconstricted zones.
The experiment was designed to test whether the ability of heparin to prevent vascular "fibrinoid" necrosis in severe hypertension is related to its effects on vascular permeability. Hypertension was produced by infusion of angiotensin II into rats for 1 or 4 hours; some rats were treated with heparin and others not. Native ferritin was used as a tracer, and small arteries of the intestine were examined by light and electron microscopy. Rats not subjected to angiotensin II were used as controls. Half were treated with heparin, and half were not. Arteries from normotensive animals showed no signs of permeability to ferritin, damage to the vessel wall, or irregularities in caliber. Vessels from hypertensive rats had alternating zones of constriction and dilatation. Ferritin penetration and vessel wall damage were found only in dilated zones; these were focal in the 1-hour experiments and more extensive in the 4-hour experiments. No differences were observed between heparin-treated and non-heparin-treated rats with respect to permeability to ferritin or to vessel wall damage. However, in the 4-hour experiments, non-heparin-treated animals had occasional fibrinlike deposits at sites of severe medial damage; these were never found in heparin-treated animals. The findings suggest that although heparin does not appear to affect vascular permeability or medial damage during acute hypertension, it may prevent polymerization of fibrin in damaged vessel walls--presumably a result of the drug's anticoagulant properties.
An 11-year-old boy developed a severe myelopathy after an eight-year history of acute lymphoblastic leukemia and numerous courses of intrathecal chemotherapy. Myelin basic protein in the cerebrospinal fluid (CSF) was elevated. Neuropathologic examination disclosed extensive microvacuolar changes in the white matter of the spinal cord. The pathogenesis of myelopathy following intrathecal chemotherapy administered by lumbar puncture includes an early effect on the myelin sheath. Serial assessment of CSF myelin basic protein levels in patients receiving intrathecal chemotherapy may be useful in the early diagnosis of this disorder.
The pathogenesis of dissecting aneurysms of the aorta is controversial. We reviewed the records of the 204 patients with aortic dissecting aneurysms who underwent autopsy at the John Hopkins Hospital, Baltimore, from 1889 to the present and compared them with age-, race-, and sex-matched controls. The results show that hypertension, Marfan's syndrome, and traumatic, atherosclerotic, or inflammatory injuries of the aortic media are factors associated with dissection. The gross and histologic findings and associated circumstances suggest that most spontaneous aortic dissections originate from tears of the inner layers of the aorta followed by intramural cleavage. In other patients, rupture of the intra-aortic course of branch arteries or vasa vasorum may lead to dissection. Thus, no pathogenetic mechanism is common to all aortic dissections.
This study examined the effects of individual differences in electrodermal lability on cardiovascular, respiratory, and electrodermal responses (EDRs) in the detection of deception. One Day 1 each of 74 subjects rested quietly for 3 min. while skin conductance was recorded. Electrodermal lability was scored for each subject, those giving frequent nonspecific EDRs being labiles and those giving few being stabiles. On Day 2, usually 1 week later, 40 of the subjects attempted to deceive a professional polygraph examiner in a field-type test. The 34 remaining subjects attempted to convince the examiner, who was blind as to each subject's condition, that they were indeed being truthful. Deception by stabile subjects was detected less frequently than was deception by labile subjects. Among truthful subjects, the more labile were falsely detected as deceptive on more questions than were their stabile counterparts. Although accuracy of detection was greatest with the EDR, the effects of lability on detection were similar for electrodermal, cardiovascular, and respiratory measures. Labiles also had a higher heart rate during the polygraph test than did stabiles.
Stroke-prone spontaneously hypertensive rats (SPSHRs) were used to test the theory that heparin treatment may prevent the development of "malignant" hypertension and fibrinoid vascular lesions in the kidney. Subcutaneous injections of heparin (100 units/100 g body weight) were given every 8 hours over a 5-week period to 12 young (10-week-old) SPSHRs. A control group of 12 SPSHRs was injected with saline. Both heparin-treated and control animals showed an incremental rise in mean systolic pressure, but the pressure was significantly lower (P less than 0.05) in the heparin-treated animals during weeks 1-4 of treatment. There were significantly fewer fibrinoid vascular lesions (P less than 0.03) in the heparin-treated group. In 7 additional heparin-treated and 7 control SPSHRs plasma and blood volumes were determined for assessment of the effects of heparin treatment. There was no significant difference in total blood volume or plasma volume between the two groups, but heparin-treated animals had lower hematocrit levels. In 8 SPSHRs direct arterial pressures were recorded for 1 hour after a single heparin injection, and no acute changes in blood pressure were observed. The results suggest that heparin treatment prevents the development of severe fibrinoid vascular lesions and also attenuates the rate of the rise in systolic blood pressure; moreover, this reduction in blood pressure is not caused by a significant reduction in blood volume or an acute hypotensive effect of heparin.
The concept has been advanced that malignant hypertension is precipitated in the rat with renal hypertension by a sudden loss of sodium in the urine. In order to test this hypothesis modest degrees of hypertension were produced in Holtzman rats by the application of a silver clip to one renal artery, not touching the opposite kidney. When the systolic blood pressure reached a level between 160 and 180 mm Hg, loss of sodium and water was induced by the administration of furosemide, given either orally over a 7-day period, or by 3 intramuscular injections over a 24-hour period. Sodium and water balance studies, blood pressure determinations, histologic assessment of blood vessels in the nonclipped kidney, and measurement of activity of the juxtaglomerular apparatus were carried out in these 2 groups and appropriate control animals. It was found that in spite of a considerable natriuresis and diuresis in furosemide-treated animals, there was neither a significant increase in the blood pressure nor development of more severe vascular lesions in the nonclipped kidney than in the kidneys of control animals.
Clinical studies have suggested that patients with Down syndrome have precocious development of pulmonary hypertension, even in the absence of congenital heart disease. To examine the pathologic basis of this impression, we studied 82 patients with Down syndrome autopsied at The Johns Hopkins Hospital from 1913 to present. The patients ranged in age from 26 hours to 25 years; 41 (50%) were female. Atrioventricular canal defect was present in 40 patients, nine of whom also had pulmonary stenosis. Eight had isolated ventricular septal defect and seven had other malformations. Histologic sections of the lung from each patient were studied and the degree of hypertensive pulmonary vascular disease graded. Age and sex-matched controls without cardiovascular manifestations, all other autopsied patients with atrioventricular canal defect not associated with Down syndrome, and age-matched patients with ventricular septal defect or other malformations were similarly studied for pulmonary vascular changes. Comparison of the 27 patients with Down syndrome and no cardiovascular malformations with normal controls showed no differences, with one notable exception: an 8-month-old child with Down syndrome had severe HPVD secondary to idiopathic pulmonary hypertension. HPVD in patients with the various cardiovascular malformations was similar for those groups with Down syndrome and those without, when HPVD was considered as a function of the patients' age and the type of malformation. We conclude that, in general, patients with Down syndrome have no predisposition to develop severe or precocious hypertensive pulmonary vascular disease.
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Extended biopsy followup of 17 relatively young men with resectable prostatic cancer treated by external supervoltage radiotherapy is presented. Although 6 of the 8 surviving patients now have negative biopsies, the over-all survival rate and the over-all incidence of negative biopsies are not so encouraging, with only 35 per cent rendered free of tumor. Thus, the role of radiotherapy in resectable prostatic carcinoma should be critically scrutinized. More accurate staging is needed. Hopefully, more sophisticated studies of diagnostic and prognostic value will be available in the near future.
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