June 1, 1994Journal of Hypertension87 citations
Mesenteric vascular smooth muscle cells from spontaneously hypertensive rats display increased calcium responses to angiotensin II but not to endothelin-1
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Key Result
In mesenteric vascular smooth muscle cells from adult spontaneously hypertensive rats, cytosolic free calcium responses to Angiotensin II are enhanced, whereas responses to endothelin-1 are reduced.
Key Points
- To evaluate differential cytosolic calcium responses to angiotensin II and endothelin-1 in mesenteric arterial smooth muscle cells from normotensive and spontaneously hypertensive rats across developmental ages.
- Isolated primary cultured, unpassaged single vascular smooth muscle cells from mesenteric arteries of Wistar-Kyoto (WKY), Wistar, and spontaneously hypertensive rats (SHR) at 3, 9, and 17 weeks of age.
- Measured cytosolic free calcium concentrations microphotometrically using the fura-2 fluorescent indicator after challenge with varying concentrations of angiotensin II and endothelin-1.
- Basal cytosolic free calcium concentration was significantly increased in mesenteric smooth muscle cells from SHR aged 9 and 17 weeks compared with age-matched WKY and Wistar control rats.
- Low-concentration angiotensin II (1 nmol/l) induced significantly higher and sustained calcium increases in SHR cells at 9 and 17 weeks, with persistent elevation beyond 100 s and significantly altered pD2 values at 17 weeks.
- Low concentrations of endothelin-1 produced significantly lower calcium responses in cells from 17-week-old SHR compared to age-matched controls, despite showing similar response kinetics across all groups.
Structured PICO
P
Population
Primary cultured unpassaged single vascular smooth muscle cells from mesenteric arteries of Wistar-Kyoto, Wistar, and spontaneously hypertensive rats aged 3, 9, and 17 weeks.
E
Exposure
Angiotensin II (Ang II) and endothelin-1
C
Comparator
Cells from age-matched normotensive WKY and Wistar rats
O
Outcome
Cytosolic free calcium concentration measured microphotometrically using fura-2 methodologysurrogate
In mesenteric vascular smooth muscle cells from adult spontaneously hypertensive rats, calcium responses to Angiotensin II are enhanced while responses to endothelin-1 are slightly reduced.
Abstract
OBJECTIVE: To determine the differential calcium responses to two vasoconstrictor peptides, angiotensin II (Ang II) and endothelin-1, in vascular smooth muscle cells derived from mesenteric arteries from young and adult normotensive and hypertensive rats. METHODS: Effects of Ang II and endothelin-1 on cytosolic free calcium concentration in primary cultured unpassaged single vascular smooth muscle cells from mesenteric arteries of Wistar-Kyoto (WKY), Wistar and spontaneously hypertensive rats (SHR) aged 3, 9 and 17 weeks were examined microphotometrically using fura-2 methodology. RESULTS: Basal cytosolic free calcium concentration was significantly increased in cells from SHR aged 9 and 17 weeks compared with cells from age-matched WKY and Wistar rats. Ang II and endothelin-1 significantly increased cell cytosolic free calcium in all rat groups at all ages. Responses to low concentrations of Ang II (1 nmol/l) were significantly higher in cells from SHR aged 9 and 17 weeks than in age-matched controls. This was confirmed in cells from rats aged 17 weeks with full concentration-response curves, which also showed that the pD2 for Ang II for WKY rats was significantly different from that of SHR. In cells from SHR at all ages Ang II-stimulated cytosolic free calcium remained persistently high, whereas in cells from WKY and Wistar rats basal levels were reached within 100 s after the maximal response. Low concentrations of endothelin-1 elicited significantly lower cytosolic free calcium responses in cells from SHR aged 17 weeks compared with age-matched controls. The time course of cytosolic free calcium responses to endothelin-1 were similar in the groups. CONCLUSIONS: In primary cultured unpassaged mesenteric vascular smooth muscle cells from adult SHR, cytosolic free calcium concentration responses to Ang II are enhanced, whereas responses to low concentrations of endothelin-1 are slightly reduced. The differential effects of these two vasoconstrictor peptides may contribute to their relative roles in modulating vascular smooth muscle cell cytosolic free calcium in SHR.
Cite This Study
Touyz et al. (1994) studied Hypertension. Angiotensin II and endothelin-1 vs. Cells from age-matched normotensive WKY and Wistar rats was evaluated on Cytosolic free calcium concentration. In mesenteric vascular smooth muscle cells from adult spontaneously hypertensive rats, cytosolic free calcium responses to Angiotensin II are enhanced, whereas responses to endothelin-1 are reduced.