The renal vasculature of Wistar Kyoto spontaneously hypertensive rats (SHR), prior to (4-5 week) and during established hypertension (21 week) and those of age-matched Wistar Kyoto normotensive rats (WKY) were morphometrically and pharmacologically studied. Under dilated conditions, the vascular resistances (RVR) of the isolated kidneys of young and adult SHR were similar to WKY. Morphometric measurements of renal vasculature indicated that the cross-sectional area of the intima and adventitia and its subcomponents were similar in adult SHR and WKY. With the exception of the preglomerular arterioles, all the renal arteries of adult SHR exhibited elevated cross-sectional quantities of total media, medial smooth muscle cells (SMCs), and extracellular space. Analysis of the SMCs indicated the presence of increased numbers of SMC layers and/or an increase in the SMC volume-to-surface area ratio in arteries sampled from adult SHR. Vascular contraction produced by infusing norepinephrine, BaCl2, angiotensin II, or by stimulating the renal nerves elevated the RVR to a greater degree in adult SHR than in WKY. The sensitivity of the renal vasculature to the various contractile agents was similar in adult SHR and WKY. When compared with WKY, prehypertensive SHR also exhibited increased cross-sectional quantities of arterial media and elevated amplitudes of RVR change in response to norepinephrine and renal nerve stimulation. However, the vascular contractile sensitivity to norepinephrine was reduced. Our results indicate that renovascular wall thickening and the hypercontractile reactivity associated with such a change precedes hypertension in SHR. In prehypertensive SHR, elevations in RVR might be counterbalanced by a decreased norepinephrine sensitivity. An increase in the norepinephrine contractile sensitivity and further vascular thickening with age could elevate the RVR and establish hypertension.

Neonatal sympathectomy using a combined treatment with antiserum to nerve growth factor and guanethidine during the first 4 weeks after birth was carried out in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Bilateral adrenal demedullation was performed in 4-week-old sympathectomized SHR and WKY rats. The development of hypertension in SHR was prevented by sympathectomy, but the blood pressure (BP) was still higher than in age-matched WKY rats. Demedullation reduced the BP of sympathectomized SHR to the same level as that of WKY rats. Heart rates of SHR and WKY rats were not affected by the treatments. Morphometric measurements of the mesenteric arteries showed that sympathectomy significantly reduced the medial mass in the mesenteric arteries of SHR, mainly through a reduction in the number of smooth muscle cell layers. In sympathectomized SHR, demedullation increased the lumen size of muscular arteries under maximally relaxed conditions, which might explain the further reduction in BP in these animals. Demedullation in sympathectomized SHR and WKY rats caused a decrease in smooth muscle cell layers in the superior mesenteric artery, but the same treatment resulted in a slight increase in the number of smooth muscle cell layers in the large and small mesenteric arteries of SHR and WKY rats. Adventitial area was increased in some mesenteric arteries of SHR and W(KY rats by sympathectomy, and demedullation caused a further increase in the size of adventitia in WKY rats. Heart weight in SHR was normalized to the level found in WKY rats by sympathectomy and demedullation. We conclude that in sympathectomized SHR, the elevated BP was maintained by the adrenal medulla. (Circulation Research 1991;69:714-721) In the spontaneously hypertensive rat (SHR), the importance of the sympathetic nervous system in the initiation and maintenance of hypertension has been emphasized by many authors,1-3 mainly because in these animals increased sympathetic activity was present in very young animals4 and destruction of the sympathetic nervous system either prevented or attenuated the development of hypertension. In our recent studies3 in which

Treatment of female spontaneously hypertensive rats (SHR) and control Wistar-Kyoto (WKY) rats with captopril was carried out by the addition of the drug in the drinking water throughout pregnancy and lactation and after weaning. At 28 weeks of age, average systolic blood pressure of treated SHR was 113±3 mm Hg, which was below that of control SHR (188±3 mm Hg) and WKY rats (124±3 mm Hg). Body weight and heart rate of the SHR were not affected by the treatment Tissue level of catecholamines was increased by captopril treatment in the superior cervical ganglia but remained unchanged in the plasma, heart, mesenteric arteries, and the adrenal glands of both SHR and WKY rats. Left ventricular weight, wall thickness, and internal diameter of the left ventricle in the SHR were reduced by the treatment Morphometric measurements of the mesenteric arteries showed that vascular alterations present in the control SHR were prevented by the treatment In the superior mesenteric artery and large mesenteric artery, smaller lumen size at maximal relaxation found in the control SHR was normalized to the level of the WKY rats. Hypertrophy of the medial wall in the superior mesenteric, large and small mesenteric arteries, and an increase in the number of smooth muscle cell layers in the large mesenteric artery of the SHR were prevented by the treatment. Perfusion study of the mesenteric vascular bed showed that reactivity of these vessels to norepinephrine was reduced, and sensitivity to norepinephrine (as determined by the effective dose that causes 50% of maximal response) was increased in the SHR by captopril treatment Sensitivity of the tail artery in response to norepinephrine was not altered by the treatment We conclude that long-term treatment with captopril of SHR before and after birth prevented the development of hypertension, structural and functional alterations of the mesenteric arteries, and cardiac hypertrophy. (Hypertension 1991;17:141-150) C hronic intracerebroventricular administration of captopril, when started in young spontaneously hypertensive rats (SHR), has been shown to attenuate the development of hypertension in these animals. -2 Such an effect was associated with a marked depression in vascular reactivity to exogenous vasoconstrictors and a potentiation of baroreceptor

Previous studies in our laboratory have shown that the renal blood vessels of 21-week-old Wistar-Kyoto spontaneously hypertensive rats exhibited thicker vascular walls than age matched Wistar-Kyoto normotensive rats. Morphometric analysis of the relaxed renovasculature revealed an increase in the cross-sectional area of the media, which in most cases was associated with an increase in the number of smooth muscle cell layers. To test if these structural changes occur in the absence of raised blood pressure, hydralazine was administered to spontaneously hypertensive rats and normotensive controls prior to and during pregnancy (100 ml/1 drinking water), and to the newborn males up to 21 weeks of age (16.9 mg/kg/day by gavage until weaning followed by 100 mg/1 in the drinking water). Treated animals were compared with untreated rats. Treatment prevented hypertension development in spontaneously hypertensive rats but did not alter the structural changes found in untreated animals with hypertension. At 21 weeks of age, hydralazine-treated spontaneously hypertensive rats had similar wall-to-lumen area ratios, medial cross-sectional areas and numbers of medial smooth muscle layers as untreated hypertensive rats while these parameters were greater in treated and untreated spontaneously hypertensive rats than in either treated or untreated normotensive controls. Withdrawal of hydralazine from 26-week-old spontaneously hypertensive rats that had been treated in utero and postnatally and had normal blood pressures throughout life resulted in the rapid onset of hypertension. Our results show that renal vascular wall thickening in spontaneously hypertensive rats occurs in the absence of high blood pressure and therefore is not a secondary effect of raised blood pressure. {Circulation Research 1988;63:534-542) B lood vessel wall thickening in hypertension has been generally thought to be the result of an adaptive response to the presence of high blood pressure.1 However, morphometric studies of renal vasculature of Wistar-Kyoto spontaneously hypertensive rats (SHR) have indicated that the cross-sectional area of the renal blood vessels increases in SHR when compared with WistarKyoto normotensive rats (WKY) prior to hypertension development.2 This suggests that renal vascular wall thickening in SHR is not a secondary alteration resulting from the presence of high blood pressure. However, some researchers have produced evidence that indicates that, within their From the

The contribution of glutaraldehyde (GA) to the effective osmolarity of GA fixatives, the osmotic reactivity of the cells after fixation in GAY and also the duration of fixation in GA on cell volume, were investigated using cultured smooth muscle cells (SMC) and spiral aortic strips. Four fixation procedures were studied. We found that GA contributes to the total effective osmolarity of the fixatives, and that the type of buffers used for the fixatives can also affect the cell volume differently during GA fixation. After GA fixation, the cells were still osmotically reactive, regardless of the buffer types for making up the GA fixatives, so that the osmolarity of the wash buffer after GA fixation is important. However, OsO4 eliminates osmotic responses, thus the osmolarity of OsO4 fixative and wash buffer have negligible influence on the cell volume. Longer fixation time up to 4 h had no effect on the cell volume.