Alteration of the Course of Hypertension in the Spontaneously Hypertensive Rat

Abstract

The blood pressure of spontaneously hypertensive rats was controlled at low normotensive levels, using antihypertensive drugs for a 6-month period beginning when the rats were 3 months of age. Treatment was then withdrawn and the rats observed for an additional 4 months, until they were 13 months of age. Treatment with antihypertensive drugs arrested the progression of the hypertension and the secondary pathology for the duration of the treatment period. Following withdrawal of drugs the blood pressure did not rise to the level of the controls of a similar age, but rather it returned to the level that existed before treatment began and then progressed at the same rate that the controls exhibited when they were 3-7 months of age. Pathological changes were found only in controls. These results indicate that, although the tendency toward hypertension is inherited, its rate of development depends on environmental factors. The hypei tension can be arrested by chemotherapeutic interventions and can be aggravated by excessive salt. The hypertension appears to be a progressive time-dependent process but is independent of biological processes associated with aging per se. Finally, control of blood pressure prevents end-organ damage. • The spontaneously hypertensive rat presents an experimental model which in many ways resembles essential hypertension in man (1). One of the great advantages of this model is that the entire life history of the disease is compressed within a period of less than 2 years. Clinically, in the treatment of patients with essential hypertension, it has been observed that, following prolonged reduction of blood

Effects of Antihypertensive Drug Therapy on the Morphology and Mechanics of Resistance Arteries from Spontaneously Hypertensive Rats

“…The treatment chosen was similar to that used by Freis et al (9) who treated SHR rats for 26 weeks. They successfully postponed the progressive course of hypertension as evidenced by a reduction of their blood pressures to the level of SHR animals 26 weeks younger, by finding an absence of vessel pathologies normal ly seen in the SHR, and by prolonging their longevity.…”

“…Drug therapy has been successfully em ployed in maintaining BP at normal levels and in reducing the incidence of fatal cardiovascular complications (9,10). The purpose of the present study was to determine whether the beneficial aspects of a particular long-term ther apeutic formula were related to a reversal of resistance vessel structural and functional char acteristics from the prior hypertensive state, or to changes elsewhere in the cardiovascular sys tem.…”

“…Our results suggest of the media was sufficient to account entirely for increased total peripheral resistance (TPR) and the vascular morphology. Observed structural changes in hypertension have included medial hypertrophy (4,8,11,17,19,24), SMC hyper plasia (2,9,22), increased connective tissue content (5,28,29), and a reduction in the number of resistance vessels (14,15). Vessels of the spontaneously hypertensive rat (SHR) have also been shown to develop greater active ten sions and to be less compliant under relaxed conditions than comparable vessels from the Wistar-Kyoto (WKY) normotensive control rat (19,22).…”

Differential effects of antihypertensive drug therapy on vascular smooth muscle cell hypertrophy, hyperploidy, and hyperplasia in the spontaneously hypertensive rat.

“…The following antihypertensive agents were added to the drinking water of drug-treated rats: chlorothiazide (Diuril, courtesy of Merck, Sharp and Dohme), 500 mg/ liter; hydralazine (Apresoline HC1, courtesy of CibaGeigy), 40 mg/liter; and reserpine (Serpasil, courtesy of Ciba-Geigy), 7 mg/liter (Freis et al, 1972). Drug-containing water was changed daily.…”

Altered in vitro uptake of norepinephrine by cardiovascular tissues of spontaneously hypertensive rats. Part 1. Mesenteric artery.

“…The SBP in WKY rats ranged from 113-130 mm Hg and in SHR from 140-200 mm Hg. 11 We used a pool of two tissues each for SHR and WKY in the first seven studies and one each for subsequent studies. Arteries with attached mesentery were preincubated for 15 minutes at 37°C in the buffer and then incubated 60 minutes in the same medium in the presence of *H-/-norepinephrine (Amersham Corporation).…”