Nitric oxide lowers the calcium sensitivity of tension in the rat tail artery

Abstract

Controversy exists as to whether a fall in the intracellular Ca2+ concentration ([Ca2+]i) is a requisite element of the vasodilatory response to nitric oxide (NO). We studied the effect of NO on the coupling between [Ca2+]i and vasoconstriction in arterial segments loaded with the [Ca2+]i‐sensitive, intracellular dye fura‐2. As data interpretation is equivocal when fura‐2 is loaded into both endothelial and smooth muscle cells, we compared results from in vitro experiments on segments of the rat tail artery in which fura‐2 and noradrenaline were applied on the luminal or adventitial side, and endothelium was removed ‘physically’ (rubbing or air) or ‘functionally’ (Nω‐nitro‐l‐arginine methyl ester). The use of air perfusion to remove endothelium is of considerable benefit since it allows paired observations in a single tissue. Fura‐2 loaded into endothelial cells but endothelial ‘contamination’ of the smooth muscle cell [Ca2+]i signal was minimal. Endogenous NO decreased vasoconstrictor responses to noradrenaline but had no effect on [Ca2+]i. Nitroglycerine decreased vasoconstrictor responses in a concentration‐dependent fashion but had no effect on [Ca2+]i. In conclusion, NO causes vasodilatation via a mechanism which is downstream of [Ca2+]i mobilization.

Age-related medial elastocalcinosis in arteries: mechanisms, animal models, and physiological consequences

“…In our laboratory's experiments on the rat, intracellular calcium is some 100,000 lower than total arterial calcium content (calculated from data in Refs. 17,60,100,119). Furthermore, it is uncertain whether changes in vascular wall intracellular calcium with age could be physiologically relevant.…”

“…Furthermore, it is uncertain whether changes in vascular wall intracellular calcium with age could be physiologically relevant. The curve relating vasoconstriction to intracellular calcium is very steep (119). However, although arterial intracellular calcium levels approximately double with age, as the sensitivity of the contractile apparatus to calcium decreases with age, the final result in terms of contractility is of minor importance (100).…”

Pertussis toxin‐sensitive Gi‐proteins and intracellular calcium sensitivity of vasoconstriction in the intact rat tail artery

“…A longitudinal tension of 0.5 g was used to restore the segment to its in situ length, the degree of retraction was 20+1% (n=46) (Tran et al, 1998). Experiments were performed in the absence of endothelium which was removed by perfusing the segment with air (0.4 ml min 71 ) plus PSS (1.5 ml min 71 ) for 10 min (intraluminal pressure 40+10 mmHg; n=46) at the beginning of the equilibration period (Tran et al, 1998). Following this procedure carbachal (10 mM) failed to relax segments precontracted with NA (3 mM).…”

“…Following this procedure carbachal (10 mM) failed to relax segments precontracted with NA (3 mM). Histological evidence of the removal of endothelium has already been published (Tran et al, 1998).…”

“…If the vasoconstrictor responses were lower than 30 mmHg for KCl or 60 mmHg for NA the segment was discarded (exclusion criteria based on Tran et al (1998). The exclusion rate was 2% (one of 46 experiments).…”