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Vascular Damage Found in Spontaneously Hypertensive
Rats Subjected to Increased Blood Pressure Variability

Martin José F. Vilela; Barbieri Neto José; Lachat João José;
Furtado Mozart R. Fortes.

University of São Paulo
Ribeirão Preto, São Paulo, Brazil.

Abstract
Introduction
Objectives
Material and Methods
Results
Conclusions
References

Abstract
Introduction:
Functional and structural vascular changes occur in the course of arterial hypertension, and they may be accelerated in the presence of increased blood pressure (BP) variability.
Objectives: To demonstrate this assertion, hypertensive crises were provoked in spontaneously hypertensive rats (SHRs) by the infusion of phenylephrine (PHE), and the thoracic/abdominal aorta was collected for histological analysis.
Material and Methods: Male animals weighing 230-300 g, and with mean arterial blood pressure (MAP) of 186,06± 2,99 mmHg (n=61) were used. Group 1 rats (n=10) had their BP elevated by the infusion of PHE at the rate of 15 m g/min/30min for two periods 24 hours apart. In group 2 (n=10), BP was elevated by the infusion of PHE at a rate of 9.63 m g/min for a first 10-min period, and at a rate of 7.25 m g/min in the subsequent 10-min periods (two weekly periods for 3 weeks). Afterwards, the rats were left for another 3 weeks without interventions, and then were sacrificed in order to obtain thoracic and abdominal aortas for microscopy.
Results: Group 1 showed MAP of 231,35± 4,51 mmHg, without aortic structural changes of significance when BP was acutely varied. Group 2, with MAP of 214.0± 5.27mmHg, after repeated hypertensive crises, showed edema of the muscular layer, microcytic degeneration of myofibrils, marked intimal thickening, with a recent mural thrombosis in one case, and aneurysmatic rupture with dissection of adventitia in another case.
Conclusions: Hypertensive rats exposed to increased variability of BP for a prolonged time become susceptible to arterial structural changes. This was not the case when BP varied acutely once.

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Introduction:

Functional and structural vascular changes occur in the course of arterial hypertension, mainly in arteries of resistance. These changes are known as hypertensive vasculopathy and they participate as anonymous answers during an initial time of arteries to vasodilatador and vasoconstrictor nature agents generating an increased vascular tonus. The functional vascular changes produce adaptative structural vascular answers of arteries with the evolution, for example muscular layer thickening and vascular remodelation that produce increased lumen-wall relation and reduced arterial lumen, situation that induces decreased tissue blood flow. These modifications are the anatomopathologic underlying of the target-organ lesions of arterial hypertension and they resemble the changes of aging. Likewise, the vessels of hypertensive, even when young, resemble the vessels of elderly without arterial hypertension. The arterial hypertension seems to cause an early aging of cardiovascular system. These modifications may be accelerated in the presence of increased blood pressure (BP) variability.

Objectives:

To demonstrate this assertion, hypertensive crises were provoked in spontaneously hypertensive rats (SHRs) by the infusion of phenylephrine (PHE), and the thoracic/abdominal aorta was collected for histological analysis.

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Material and Methods:

Male animals weighing 230-300 g, and with mean arterial blood pressure (MAP) of 186,06± 2,99 mmHg (n=61) were used. After anesthesia with ether, passed a catheter in a left carotid artery and right jugular vein for register of blood pressure and infusion of drugs, respectively.
Group 1 rats (n=10) had their BP elevated by the infusion of PHE at the rate of 15 m g/min/30min for two periods 24 hours apart. In group 2 (n=10), BP was elevated by the infusion of PHE at a rate of 9.63 m g/min for a first 10-min period, and at a rate of 7.25 m g/min in the subsequent 10-min periods (two weekly periods for 3 weeks). Afterwards, the rats were left for another 3 weeks without interventions, and then were sacrificed in order to obtain thoracic and abdominal aortas for microscopy. Group 3 rats (n=10), used for control, were infused with isotonic saline solution.
The tissue samples were fixed in formol 10% and in glutaraldehyde 2,5% for inclusion in paraffin (were stained with Mallory trichrome) and inclusion in araldite glue (were stained with toluidine blue 1%), respectively.

Results:

Group 1 showed MAP of 231,35± 4,51 mmHg, without aortic structural changes of significance when BP was acutely varied, except for interstitial edema of the muscular layer in the samples included in araldite glue (figure 1). Group 2, with MAP of 214.0± 5.27mmHg, after repeated hypertensive crises, showed edema of the muscular layer, microcytic degeneration of myofibrils, marked intimal thickening (figure 2A) with a recent mural thrombosis in one case (figure 2B), and aneurysmatic rupture with dissection of adventitia in other cases (figure 2 C). Group 3 showed MAP of 172,0 ± 9,24 mmHg without aortic structural changes of significance.

Figure 1

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Tissue sample of thoracic/abdominal aorta, included in araldite and stained with toluidine blue, showing: A – Aorta of group 3 rat with normal aspect hystologic (560 x); B – Aorta of group 2 rat with edema of muscular layer (white arrow) (560 x). * Arterial lumen

Figure 2

fig2.jpg (40156 bytes)

Tissue sample of the thoracic/abdominal aorta, included in paraffin and stained with Mallory trichrome, in group 2 SHR, showing: A – General view of atherosclerotic plate with edema of muscular layer, marked intimal thickening, and recent under-intimal hemorrhage (340 x); B – Recent mural thrombosis (,), intimal thickening and disorganization of elastic fibers of muscular layer (340 x); C – Aneurysmatic rupture with dissection of adventitia (**) (135 x). * Arterial lumen

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Conclusions:

Hypertensive rats exposed to increased variability of BP for a prolonged time become susceptible to arterial structural changes. This was not the case when BP varied acutely once. Some of structural changes (intimal thickening and muscular layer hypertrophy) resemble natural arterial aging.

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References:

1 - Bohlen HG. Localization of vascular resistance changes during hypertension. Hypertension 1986; 8: 181-183.
2 - Chobanian A . Adaptive and maladaptive responses of the arterial wall to hypertension. Hypertension 1990; 15: 666-674.
3 - Omboni S.; Parati G.; Frattola A, et al. : Spectral and sequence analysis of finger blood pressure variability: Comparison with analysis of intra-arterial recordings. Hypertension 1993; 22: 26-33.

Technical assistance: Maurício R. Arantes, Adalberto V. Verceze, Rosângela O Lopes, Eloísa M. Russo.
Supported by CAPES

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Questions, contributions and commentaries to the Authors: send an e-mail message (up to 15 lines, without attachments) to hbp-pcvc@pcvc.sminter.com.ar , written either in English, Spanish, or Portuguese.


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Bioengineering
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Update
Mar/05/2000


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