Experimental hypertension.

Abstract

Several interventions are used to induce hypertension in the experimental animal. The three most used interventions are renal ischemia, mineralocorticoid excess, and genetic manipulation. The sequence of events leading from these initiating manipulations to the elevated arterial pressure is being explored to define the mechanism responsible for hypertension. The following mechanisms are currently extensively evaluated: Pressor and depressor factors of renal origin, neurogenic regulation, circulating humoral factors, vessel wall hypertrophy, and membrane transport abnormality. The experimental models of hypertension hold great promise in providing an understanding of the mechanisms and developing effective treatment in clinical hypertension. (Hypertension 1991;17[suppl I]:I-39-I-44) W ith over 30,000,000 cases of hypertension in the United States, opportunity for clinical research is unlimited. Yet a major source in understanding this disease comes from the use of experimental models of hypertension. Evidence for the magnitude of the contribution made by experimental hypertension is seen in the number of articles published in the past 2 years in our two major journals on hypertension. In 1987 and 1988, Hypertension published 118 clinical and 166 experimental articles, and the Journal of Hypertension published 113 clinical and 108 experimental articles. Based on these data, 54% of our information about hypertension is derived from experimental studies.Historically, "The greatest single advance in the experimental production of the condition resembling that of hypertension in man was a convincing demonstration by Goldblatt, Lynch, Hanzel, and Summerville that persistent hypertension could be produced in dogs" (Sir George Pickering).1 In 1934, Goldblatt et al 2 showed that partial constriction of the renal artery and removal of the opposite kidney produce persistent hypertension (one-kidney, one clip hypertension [1K1C]) in dogs. Differing from dogs, the constriction of one renal artery in rats results in hypertension regardless of the presence or absence of the contralateral kidney. The third major model of experimental hypertension was introduced by Smirk and Hall 6 in 1958, when they developed a colony of hypertensive rats by breeding rats with above-average tail blood pressure. This strain of genetically hypertensive rats is now known as the New Zealand strain.As with mineralocorticoid hypertension, the major impetus for the study of genetic hypertension came later. In 1963, Okamoto and Aoki 7 introduced the spontaneously hypertensive rat (SHR), which is presently the most studied experimental model of hypertension. These investigators commenced their colony by mating a male Wistar-Kyoto (WKY) rat that had elevated blood pressure (145-175 mm Hg) with a female WKY rat that had slightly higher than average blood pressure (130-140 mm Hg). In the Fj and subsequent generations, they conducted brothersister inbreeding of the siblings selected for having the highest pressures in each litter. After the third generation,...

Intraocular pressure measurement in the conscious rat

“…Its anterior segment anatomy, especially the aqueous outflow system, is similar to that in the primate (Morrison et al 1995). The present study was stimulated by the rat paradigm in circulation research: following the introduction, in 1932, of the tail-cuff method of measuring arterial pressure in the conscious, unsedated animal, the rat was propelled into prominence for a broad and still growing array of studies (Bohr & Dominiczak 1991). A reliable method for measuring IOP in the concious rat now makes this animal available for IOP research.…”

Nitric oxide and coronary vascular endothelium adaptations in hypertension

“…The spontaneously hypertensive rat (SHR) model has been particularly useful since several defining characteristics of the SHR are similar to those observed in human essential hypertension including hemodynamic abnormalities, humoral and sympathetic nervous system involvement, renal abnormalities and vascular cellular adaptations. [23][24][25][26][27][28] For example, even though SHR can have similar coronary blood flow compared to their normotensive counterpart Wistar-Kyoto rats (WKY) on a ventricular mass-corrected basis, 13 SHRs have higher coronary vascular resistance (CVR) over a wide pressure range, 14,19 and higher minimal CVR (lower maximal conductance) during maximal coronary vasodilation. 13,16 Changes in coronary hemodynamics accompanying hypertension occur as a result of both structural and functional adaptations in the coronary vasculature.…”

Amlodipine modulation of analgesic effect of non-steroidal anti-inflammatory drugs in rheumatoid arthritis, comorbid with arterial hypertension

“…In the animals (200 rats, salt drink with free access to it for 21 days) arterial hypertension was induced by salt loading (Bohr & Dominiczak, 1991;Badyal et al, 2003;Dornas & Silva, 2011).…”