Invited Symposium: Hypertension II: Hypertension and Vascular Control
Role of the Renal Microvasculature in Hypertension.
The control of hypertension by drugs which inhibit the renin-angiotensin system points to the critical role of this system in the maintenance of hypertension (4). Furthermore, the intrarenal actions of angiotensin II are importantly involved in the long term control of arterial blood pressure (5). Two of the most important intrarenal actions of angiotensin II include constriction of the microcirculation and stimulation of tubular sodium transport (5). Chronic infusion of angiotensin II at rates too low to have an initial pressor effect cause a gradual elevation in blood pressure over several days. During the development of angiotensin II infused hypertension pressor responses to acute administration of angiotensin II are potentiated, "autopotentiation"(4). In the early stages of angiotensin II infused hypertension an increased responsiveness to angiotensin II but not norepinephrine has been demonstrated in the isolated mesenteric vasculature and aorta (4). The current studies were performed to determine if an enhanced renal microvascular tone and responsiveness to vasoconstrictors occurs during the development of angiotensin II-induced hypertension.
1.) Assess the effects of angiotensin II-induced hypertension on renal microvascular dimensions and responses to changes in perfusion pressure.
2.) Determine if angiotensin II infused hypertensive rats have enhanced renal microvascular reactivity to angiotensin II, "autopotentiation".
Materials and Methods
Induction of Angiotensin II Infused Hypertension.
In Vitro Perfused Juxtamedullary Preparation.
Interlobular and afferent arteriolar diameter were measured using a digital image shearing monitor which was calibrated by a stage micrometer and measurements were reproducible within 0.5 µm. In the first series of experiments, renal perfusion pressure was lowered to 80 mmHg and the pressure-diameter relationship determined. Following the 15 min equilibration period, perfusion pressure was varied in steps form 80 to 120 to 160 mmHg. In the second series of experiments, measurements of resting afferent arteriolar diameters were made at a renal perfusion pressure of 100 mmHg. Angiotensin II (0.1-10 nM) or norepinephrine (10 nM-1µM) were administered by superfusion and diameter changes monitored for 5 minutes. Renal perfusion pressure was increased to 150 mmHg and the response to angiotensin II redetermined in animals that received angiotensin II infusion for 11-13 days.
Development of Hypertension.
Enhanced Renal Microvascular Tone in Angiotensin II Induced Hypertension. Renal microvascular responses to increasing renal perfusion pressure were observed utilizing the in vitro juxtamedullary nephron preparation. At a renal perfusion pressure of 80 mmHg interlobular and afferent arteriolar diameters of normotensive animals averaged 28 ± 1 and 18 ± 1 µm; respectively. Diameters of the interlobular arteriole at renal perfusion pressures of 80, 120, and 160 mmHg were 12-20% smaller in hypertensive animals; however, arterioles from both groups responded to increases in renal perfusion pressure with similar 21-25% decreases in diameter (Figure 3).
Enhanced Renal Microvascular Responsiveness to Angiotensin II in Hypertensive Animals. Angiotensin II infused hypertensive rats studied at 11-13 days had an enhanced afferent arteriolar responsiveness to angiotensin II at renal perfusion pressures of 100 and 150 mmHg (Figure 4).
Afferent arteriolar responses to angiotensin II and norepinephrine at a renal perfusion pressure of 100 mmHg were observed in angiotensin II infused hypertensive’s and normotensive controls 5-7 days following osmotic minipump implantation. Angiotensin II (10 nM) decreased afferent arteriolar diameter by 27 ± 3% in the 5-7 say hypertensive group compared to 20 ± 2% in normotensive controls. In contrast, the afferent arteriolar response to norepinephrine was not altered after 5-7 days of angiotensin II infusion (Figure 5).
Discussion and Conclusion
1.) Angiotensin II infused hypertensive rats have reduced interlobular diameters and maintained reactivity to changes in renal perfusion pressure.
2.) Afferent arterioles of hypertensive rats infused with angiotensin II for 11-13 days have an enhanced responsiveness to angiotensin II, "autopotentiation".
3.) The afferent arteriolar response to angiotensin II but not norepinephrine is enhanced following 5-7 days of angiotensin II-induced hypertension.
These data demonstrate an elevated renal microvascular tone and enhanced preglomerular reactivity which is selective for angiotensin II during the early stages of hypertension following infusion of angiotensin II. Thus, excessive renal vasoconstriction is a contributing factor to the initial defect in renal function leading to the development of hypertension.
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|Imig, J.D.; (1998). Renal Microvascular Reactivity to Angiotensin II is Enhanced in Angiotensin II-Induced Hypertension. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/boegehold/imig0781/index.html|
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