Objective: The importance of sympathetic innervation for the development of structural changes in the cerebral arteries of hypertensive animals was studied. Design: Sympathetic denervation was induced with combined treatment from birth of antibody against nerve growth factor and guanethidine. Previous studies from our laboratory showed that this procedure not only caused a permanent denervation of the mesenteric arteries, but also prevented the development of hypertension in spontaneously hypertensive rats (SHR). Methods: Morphometric measurement of the structural changes was carried out in the basilar, superior cerebellar, posterior cerebral and middle cerebral arteries from 28-week-old SHR, stroke-prone SHR, and normotensive Wistar-Kyoto rats. The results were compared with those obtained from cerebral arteries of sympathectomized rats. Results: Total vascular wall cross-sectional area was significantly larger in the basilar and superior cerebellar arteries from hypertensive rats compared with normotensives. The change was characterized by an increase in the number of smooth muscle cell layers. There were also differences between the two hypertensive groups in some arteries. Sympathetic denervation attenuated the development of hypertension and vascular changes in some arteries. There was a positive linear correlation between blood pressure and medial cross-sectional area, and between blood pressure and the number of smooth muscle cell layers for the four arteries analysed. Conclusion: Sympathetic nerves have a trophic influence upon the remodelling of some cerebral arteries during the development of genetic hypertension.
Abstract The effects of chronic treatment with an AT 1 receptor antagonist (L-158,809) on hypertension development and cardiovascular changes were studied in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). L-158,809 treatment (0.6 mg/kg PO) was initiated at 3 weeks of age and lasted 12 weeks, to 15 weeks of age. The treatment prevented hypertension development in the SHR (systolic blood pressure, BP, of 136±1 mm Hg compared with 198±3 mm Hg in control SHR), and lowered the BP of WKY (99±2 vs 128±1 mm Hg in control WKY). Treatment significantly reduced the heart weight in SHR and WKY. Ten weeks after treatment withdrawal (25 weeks of age), BP had increased in SHR and WKY to 172±8 and 117±3 mm Hg, respectively. Body weight and kidney weight were not affected by the treatment. Mesenteric arteries from treated SHR were less responsive than control SHR arteries to periarterial nerve stimulations at transmural pressures higher than 80 mm Hg (15 and 25 weeks). Control WKY arteries were less responsive than control SHR arteries at almost all transmural pressures tested (15 weeks) and to pressures greater than 80 mm Hg (25 weeks). Pretreatment of arteries with 10 −8 mol/L angiotensin II enhanced their response to nerve stimulation in vessels from control SHR and WKY (25 weeks) but not from treatment-withdrawn SHR and WKY. Treatment did not alter arterial reactivity in response to norepinephrine. Alteration in arterial structure due to L-158,809 treatment was found only when measured at a transmural pressure of 100 mm Hg. In conclusion, L-158,809 was effective in preventing hypertension during the treatment period, in reducing hypertension severity during the withdrawal period, and in persistently decreasing the reactivity of the arteries.
We have on several occasions studied the nasal respiratory epithelium of an infant with hyaline membrane disease that evolved into bronchopulmonary dysplasia and observed an association between the...
This study tested the hypotheses that renal medullary blood flow (MBF) in spontaneously hypertensive rats (SHR) has enhanced responsiveness to angiotensin (ANG) II and that long-term treatment with enalapril can correct this. MBF, measured by laser Doppler flowmetry in anesthetized rats, was not altered significantly by ANG II in Wistar-Kyoto (WKY) rats, but was reduced dose dependently (25% at 50 ng · kg −1 · min −1 ) in SHR. Infusion of N G -nitro-l-arginine methyl ester (l-NAME) into the renal medulla unmasked ANG II sensitivity in WKY rats while l-arginine given into the renal medulla abolished the responses to ANG II in SHR. In 18- to 19-wk-old SHR treated with enalapril (25 mg · kg −1 · day −1 when 4 to 14 wk old), ANG II did not alter MBF significantly, but sensitivity to ANG II was unmasked after l-NAME was infused into the renal medulla. Endothelium-dependent vasodilation (assessed with aortic rings) was significantly greater in treated SHR when compared with that in control SHR. These results indicate that MBF in SHR is sensitive to low-dose ANG II and suggest that this effect may be due to an impaired counterregulatory effect of nitric oxide. Long-term treatment with enalapril improves endothelium-dependent vascular relaxation and decreases the sensitivity of MBF to ANG II. These effects may be causally related to the persistent antihypertensive action of enalapril in SHR.
Morphometric measurements of three categories of mesenteric vessels (representing elastic, muscular and arteriolar vessels) from prehypertensive spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY) were carried out at the light and electron microscope levels. Structural alterations of the blood vessels were already present in the SHR, even though the blood pressure was not yet elevated as compared with age-matched WKY. No change was found in the elastic vessels (superior mesenteric artery). Among the muscular arteries (i.e. large mesenteric arteries), the increase in vessel wall cross-sectional area was due to the increase in the intima, media and adventitia. Increase in media was due to hyperplasia of the smooth muscle cells. The smooth muscle cells were not hypertrophied. Nerve density was also higher in the large mesenteric arteries of SHR. In the arteriolar vessels (i.e. small mesenteric arteries), wall to lumen ratio, as well as media to lumen ratio, were increased in the SHR. The number of smooth muscle cell layers was also increased. In all these vessel types, the cross-sectional area of the lumen under maximal relaxation was similar between SHR and WKY, except in small mesenteric arteries where the lumen was smaller in the SHR. Our results suggest that structural alteration of the blood vessels at the prehypertensive phase may be one of the contributing factors leading to the development of hypertension in the SHR.
Recent epidemiological studies have shown that there is an increased risk of obesity and hypertension in children born to women who smoked during pregnancy. The aim of this study was to examine the effect of fetal and neonatal exposure to nicotine, the major addictive component of cigarette smoke, on postnatal adiposity and blood vessel function.Female Wistar rats were given nicotine or saline (vehicle) during pregnancy and lactation. Postnatal growth was determined in the male offspring from weaning until 26 weeks of age. At 26 weeks of age, fat pad weight and the function of the perivascular adipose tissue (PVAT) in the thoracic aorta and mesenteric arteries were examined.Exposure to nicotine resulted in increased postnatal body weight and fat pad weight and an increased amount of PVAT in the offspring. Contraction of the aorta induced by phenylephrine was significantly attenuated in the presence of PVAT, whereas this effect was not observed in the aortic rings from the offspring of nicotine-exposed dams. Phenylephrine-induced contraction without PVAT was not different between saline- and nicotine-exposed rats. Transfer of solution incubated with PVAT-intact aorta to PVAT-free aorta induced a marked relaxation response in the rats from saline-exposed dams, but this relaxation response was significantly impaired in the rats from nicotine-exposed dams.Our results showed that prenatal nicotine exposure increased adiposity and caused an alteration in the modulatory function of PVAT on vascular relaxation response, thus providing insight into the mechanisms underlying the increased prevalence of obesity and hypertension in children exposed to cigarette smoke in utero.
