The rat with spontaneous genetic hypertension is not a suitable model of human essential hypertension.

McGiff, John C.; Quilley, C P

doi:10.1161/01.res.48.4.455

Cited by 46 publications

(15 citation statements)

References 49 publications

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“…Prostaglandins and other arachidonic acid (AA) metabolites originating within the kidney participate in several mechanisms that can affect blood pressure by contributing to the regulation of extracellular fluid volume and renal hemodynamics. 1 ' 2 Of the variety of AA metabolites generated by the kidney, those arising from cytochrome P450-dependent monooxygenases also demonstrate the requisite biological activity to influence blood pressure. Several of these eicosanoids generated by a cytochrome P450 monooxygenase system operating intrarenally have been shown to affect vascular tone 3 ' 4 and to be capable of modulating Na + ,K + -ATPase activity.…”

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Chronic treatment with tin normalizes blood pressure in spontaneously hypertensive rats.

et al. 1991

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We have reported that short-term treatment of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats with stannous chloride (SnCl 2 ), which selectively depletes renal cytochrome P4S0, restores blood pressure to normal in young but not in adult SHR, and is without effect on blood pressure of either young or adult WKY rats. We report in the present study that chronic treatment with SnCl 2 , begun at age 5 weeks, prevented the development of hypertension in SHR over a period of 15 weeks at which time they were killed. Suspension of SnCl 2 treatment after 8 weeks (i.e., at age 13 weeks) did not result in return of blood pressure to hypertensive levels in SHR. Age-matched WKY rats were not affected by tin treatment These findings provide additional evidence that administration of tin, which stimulates heme oxygenase, thereby producing depletion of cytochrome P450, restores blood pressure to normal levels in SHR. {Hypertension 1991;17:776-779) T he kidney, through its endocrine and excretory function, exerts a key role in the regulation of blood pressure. Prostaglandins and other arachidonic acid (AA) metabolites originating within the kidney participate in several mechanisms that can affect blood pressure by contributing to the regulation of extracellular fluid volume and renal hemodynamics. 1 ' 2 Of the variety of AA metabolites generated by the kidney, those arising from cytochrome P450-dependent monooxygenases also demonstrate the requisite biological activity to influence blood pressure. Several of these eicosanoids generated by a cytochrome P450 monooxygenase system operating intrarenally have been shown to affect vascular tone 3 ' 4 and to be capable of modulating Na + ,K + -ATPase activity. 56 To define possible relations between the renal cytochrome P450 system and regulation of blood pressure, we studied spontaneously hypertensive rats (SHR), the animal model most resembling human hypertension. In the SHR, renal Received September 21, 1990; accepted in revised form February 15, 1991. mechanisms are thought to play a decisive role in elevating blood pressure. 78 We have obtained evidence to support the hypothesis that eicosanoids generated by the renal cytochrome P450 system participate in the elevation of blood pressure. These renal metabolites are generated in increased amounts only by the young SHR, when compared with either the mature SHR or with age-matched normotensive Wistar-Kyoto (WKY) rats, during the developmental phase of hypertension from the fifth to the 13th week. 9 We have been able to restore blood pressure to normal levels in young 7-week-old SHR during the developmental stage of hypertension with short-term treatment with stannous chloride (SnCl 2 ). SnCl 2 induces heme oxygenase activity.10 Increased activity of heme oxygenase accelerates heme degradation, including that associated with cytochrome P450, thereby impairing the ability of the renal cytochrome P450 system to form eicosanoids 10 and, presumably, to metabolize other local and circulating hormones t...

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Chronic treatment with tin normalizes blood pressure in spontaneously hypertensive rats.

et al. 1991

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“…3 Actually, this assumption has been challenged. 4 Moreover, the proliferation of different strains with apparently different characteristics makes the presence of genetic hypertension with its clinical manifestations an uncertain criterion for considering a spontaneously hyper-tensive strain as a model. A comparison of precise, quantitative biological indexes would be more suitable to prove or disprove the similarity of essential and spontaneous hypertension.…”

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Similarities of essential and spontaneous hypertension. Volume and number of blood cells.

Bruschi¹,

Minari²,

Bruschi³

et al. 1986

Hypertension

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SUMMARY Spontaneously hypertensive rats have long been used as an animal counterpart of human essential hypertension. The validation of this strain as a model rests mainly on the "clinical" similarity of the two syndromes, but it has scarcely been founded on numerical comparison of measurable parameters. We investigated three hematological indexes previously recognized to be altered in spontaneously hypertensive rats: the single-cell volume of erythrocytes, the single-cell volume of platelets, and the erythrocyte number. Erythrocyte volume was lower by 7%, platelet volume was higher by 12%, and erythrocyte count was higher by 22% in spontaneously hypertensive rats in comparison with Wistar-Kyoto controls. More unexpectedly, it was found that erythrocyte volume is lower by 2%, platelet volume is higher by 3%, and erythrocyte number is higher by 6% in essential hypertensive subjects when compared with normotensive healthy subjects. These results, combined with previously reported blood cell alterations in subjects and rats, reinforce the evidence of a biological similarity between essential and spontaneous hypertension. of essential hypertension requires no special emphasis. Spontaneously hypertensive rats (SHR) of the Okamoto-Aoki strain are the most widely accepted such model at the present time. Since their introduction, considerable evidence has been accumulated that essential and spontaneous hypertension share many common clinical features (e.g., genetic transmission, natural history, pathology, complications); however, this is a rather vague and unsatisfactory assessment of the possibility that the two syndromes represent the same disease in different species. '" 3 Actually, this assumption has been challenged. 4 Moreover, the proliferation of different strains with apparently different characteristics makes the presence of genetic hypertension with its clinical manifestations an uncertain criterion for considering a spontaneously hyper-

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“…7 -*• l3 ' M Although immobilization for vital microscopy reinforces a number of uncertainties such as the effects of general anesthesia, 13 the relevance of the model syndrome to humans, 16 or surgical intervention for exteriorizing tissues for microscopy, 17 the insight afforded by the intravital approach provides basic information not available by any other method. Hopefully in the future, as a background of detailed information sharpens our focus, indirect methods applicable to man can be introduced.…”

Section: Microvascular Bed In Hypertension/zwei/ac/i M Lmentioning

confidence: 99%

“…By far the largest number of investigations have utilized the spontaneously hypertensive rat (SHR) an inbred offshoot of the Wistar-Kyoto strain. 21 The applicability of this model to essential hypertension in humans has been questioned 16 since the precise etiology of the syndrome in these genetically predisposed animals has not been established.…”

Section: Microvascular Bed In Hypertension/zwei/ac/i M Lmentioning

confidence: 99%

The microcirculation in experimental hypertension. State-of-the-art review.

Zweifach¹

1983

Hypertension

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SUMMARY Information concerning the microcirculation has been obtained largely by intravital microscopy of selected tissues in the rat-skeletal muscle and splanchnic viscera, as well as in the cheek pouch of the hamster. The data for the most part pertain to the spontaneous form of hypertension in the SHR strain of rats and renovascular forms of the disease involving surgical manipulation of the kidney or its blood supply. Direct measurements of pressure and flow in exteriorized skeletal muscle preparations reveal a 2-to 3-fold increase in resistance to flow. An increase in resistance appears in the terminal arterioles and their precapillary branches as early as at 4 weeks of age for SHR animals and is progressively exacerbated in older more mature animals. The increase in microvascular resistance appears to develop as a consequence of neurogenic and humoral mechanisms which act initially on larger arterioles (50-100 /xm) and subsequently on the peripheral arterioles (15-25 /xm in diameter). The smaller arterioles not only show an increased tone under steady state conditions but what can be referred to as a functional rarefaction in which 30% to 50% of the precapillary extensions of the arterioles are shut off for varying periods from the active muscle circulation. Structural rarefaction (a reduced number of arterioles) is seen only in the late stages of the SHR syndrome and can account for a small portion of the increase in peripheral resistance. The cause and effect relationship between the microvascular changes and the associated elevation in systemic pressure cannot be unequivocally demonstrated in intravital preparations. Hypertension induced by different experimental modalities does not have a consistent microcirculatory counterpart, leading to the conclusion that depending on the precise mechanisms involved in the initiation of the syndrome, microcirculatory derrangements can arise as either initiating or secondary phenomena. Tissue pathology is uniformly associated with a reduction in arterial supply, and uneven distribution of blood and red cell hematocrit in the network proper. On the postcapillary side, there is a trend for venular tortuosity and distension.

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The rat with spontaneous genetic hypertension is not a suitable model of human essential hypertension.

Cited by 46 publications

References 49 publications

Chronic treatment with tin normalizes blood pressure in spontaneously hypertensive rats.

Chronic treatment with tin normalizes blood pressure in spontaneously hypertensive rats.

Similarities of essential and spontaneous hypertension. Volume and number of blood cells.

The microcirculation in experimental hypertension. State-of-the-art review.

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