Direct measurements of arterial pressure, stroke volume (SV), and cardiac output (CO) were obtained in ether-anesthetized rats with established spontaneous hypertension (SHR) treated with alpha-methyldopa and compared to both untreated hypertensive and normotensive Wistar-Kyoto (WKY) rats. Left ventricular pumping ability was determined by the maximum levels of SV and CO reached during rapid intravenous volume loading with blood. Treatment with methyldopa reduced the SHR arterial blood pressure (average 57 mm Hg) and reversed the cardiac hypertrophy toward normal. In comparison to untreated SHR, therapy increased heart rate and CO and decreased peripheral resistance. During volume-loading, the levels of SV and CO at matched left ventricular end-diastolic pressures were significantly higher in treated vs untreated SHR. To evaluate the role of blood pressure in the improved peak pumping ability observed in treated rats, a phenylephrine infusion was used to equalize pressures while repeating cardiac function studies. In normotensive WKY and untreated SHR, left ventricular pump function was not greatly affected. A pronounced depression in peak SV and peak CO was observed only in treated SHR. The data indicate that treatment with methyldopa is associated with improved ventricular function in part related to the reduction in arterial pressure.

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SUMMARY Collagen synthesis, content, and concentration were determined in die hypertrophied intima media of thoracic aortas from 10-, 15-, and 20-week-old spontaneously hypertensive rats (SHR). Although the rates of aortic collagen synthesis declined with age, the dry weight of the Intima media and the total collagen content increased proportionally. Collagen concentration thus remained unchanged. Methyldopa was administered orally to SHR when they were 12 to 15 weeks of age, when their body weights were Identical to the untreated group. Blood pressure and the degree of aortic medial hypertrophy, judged by medial dry weight per kilogram body weight, were significantly lower compared with untreated SHR. Collagen synthesis was likewise decreased to a mean rate not significantly higher than age-matched nonnotensive Wistar-Kyoto controls. This reduction in collagen synthesis, however, was not sufficient to decrease measurably the total collagen content of the aortas compared with untreated SHR. Since medial dry weights were lower in the treated rats, collagen concentration in aortas from SHR given methyldopa for 3 weeks was actually increased. The increase in collagen concentration also suggests that medial hypertrophy was reversed. A common structural response to hypertension of various etiologies is a thickening of the medial layer of both large and small arteries. Medial thickening is due to hyperplasia and hypertrophy of smooth muscle cells with concomitant increases in collagen, elastin, glycosaminoglycans, electrolytes, and water. 1 -3 Increases in the total arterial content of these components is not always accompanied by an actual increase in the concentration expressed per unit of wet or dry weight, deoxyribonucleic acid (DNA), or protein. Therefore, a distinction between alterations in arterial content and concentration is of considerable importance because it is directly relevant to our understanding of the mechanisms underlying the development of cardiovascular hypertrophy. Wolinsky, 2 for example, showed that collagen content, but not concentration, was increased in the thickened media of thoracic aortas from renal hypertensive rats. Sen et al.* likewise showed that total collagen content but not concentra- tion was increased in hypertrophied ventricles of young adult spontaneously hypertensive rats (SHR) compared with normotensive controls. The latter also demonstrated that reversal of cardiac hypertrophy in SHR by treatment with methyldopa' 14 was not accompanied by a parallel decrease in myocardial collagen content. This finding may have some bearing upon the functional consequences of cardiac hypertrophy as well as its reversal. Skelton and Sonnenblick* have suggested that alterations in cardiac collagen might influence ventricular compliance. Studies by Spech et al." and Pfeffer et al. 7 provide additional, albeit indirect, evidence linking alterations in collagen metabolism with pump function.The purpose of the present experiments was to determine whether the arterial wall in spontaneously hyper...

To elucidate whether the presence of angiotensin II immunoreactivity (ANG II-ir) in the cerebrospinal fluid (CSF) of the dog is in part due to passage of the peptide across the CSF-blood-brain barrier, [Ile5] angiotensin II (ANG II) was infused intravenously for 7 days in conscious, trained dogs at a rate of 10 micrograms/kg/day. Mean arterial pressure (MAP) and heart rate were monitored each day, and samples of arterial blood and CSF (with a catheter secured into the cisterna magna) were drawn at regular intervals for determination of catecholamine levels, ANG II-ir, and electrolyte levels. Within 2 days after ANG II infusion, MAP stabilized at 35 +/- 1 mm Hg (mean +/- SE, p less than 0.001) above control values. The hypertension was associated with bradycardia, suppressed plasma renin activity, and a fall in both plasma and CSF Na+ concentrations. These changes coincided with a considerable and sustained decrease in the levels of plasma and CSF norepinephrine. On the other hand, levels of epinephrine and K+ in the two compartments remained unchanged. Although concentration of ANG II-ir in plasma was augmented markedly (368% above control values, p less than 0.001), ANG II-ir in the CSF remained within the low values measured in the control period.(ABSTRACT TRUNCATED AT 250 WORDS)

Recent evidence has suggested that cardiac factors may play a role in the evolution of arterial hypertension. To test the possibility that an increase in cardiac-performance can lead to a sustained increase in systemic blood pressure, we electrically stimulated the left stellate ganglion of six conscious dogs continuously for a 7-day period and monitored cardiac output and arterial blood pressure. In all six dogs, stimulation elicited an abrupt rise in systemic blood pre-sure that was entirely due to rise in cardiac output that lasted at least 6 hours. After 1 day of continuous stimulation, cardiac output retured to control values, but blood pressure remained elevated. After 7 days of stimulation, blood pressure was increased by an average of 25 mm Hg and peripheral resistance by 35 plus and minus 4%. Measurements of blood volume, plasma renin activity, circulating catecholamines (three of the six dogs), and sodium balance showed that none of these factors could explain the development pf this sustained hypertension. Pharmacologic blockade with phenoxybenzamine prevented in large part the rise in blood pressure in short-term stellate ganglion stimulations, whereas propranolol had very little effect on the pressor response, although it nearly abolished the increase in cardiac output. The data indicate that continuous stimulation of the stellate ganglion in conscious dogs leads to substained rises in both blood pressure and peripheral resistance; these changes are apparently mediated by increased activity of the sympathetic nervous system.