Regulation of arterial diameter and wall [Ca2+] in cerebral arteries of rat by membrane potential and intravascular pressure

1. The regulation of intracellular [Ca(2+)] in the smooth muscle cells in the wall of small pressurized cerebral arteries (100–200 μm) of rat was studied using simultaneous digital fluorescence video imaging of arterial diameter and wall [Ca(2+)], combined with microelectrode measurements of arterial membrane potential. 2. Elevation of intravascular pressure (from 10 to 100 mmHg) caused a membrane depolarization from -63 ± 1 to -36 ± 2 mV, increased arterial wall [Ca(2+)] from 119 ± 10 to 245 ± 9 nm, and constricted the arteries from 208 ± 10 μm (fully dilated, Ca(2+) free) to 116 ± 7 μm or by 45 % (‘myogenic tone’). 3. Pressure-induced increases in arterial wall [Ca(2+)] and vasoconstriction were blocked by inhibitors of voltage-dependent Ca(2+) channels (diltiazem and nisoldipine) or to the same extent by removal of external Ca(2+). 4. At a steady pressure (i.e. under isobaric conditions at 60 mmHg), the membrane potential was stable at -45 ± 1 mV, intracellular [Ca(2+)] was 190 ± 10 nm, and arteries were constricted by 41 % (to 115 ± 7 μm from 196 ± 8 μm fully dilated). Under this condition of -45 ± 5 mV at 60 mmHg, the voltage sensitivity of wall [Ca(2+)] and diameter were 7.5 nm mV(−1) and 7.5 μm mV(−1), respectively, resulting in a Ca(2+) sensitivity of diameter of 1 μm nm(−1). 5. Membrane potential depolarization from -58 to −23 mV caused pressurized arteries (to 60 mmHg) to constrict over their entire working range, i.e. from maximally dilated to constricted. This depolarization was associated with an elevation of arterial wall [Ca(2+)] from 124 ± 7 to 347 ± 12 nm. These increases in arterial wall [Ca(2+)] and vasoconstriction were blocked by L-type voltage-dependent Ca(2+) channel inhibitors. 6. The relationship between arterial wall [Ca(2+)] and membrane potential was not significantly different under isobaric (60 mmHg) and non-isobaric conditions (10–100 mmHg), suggesting that intravascular pressure regulates arterial wall [Ca(2+)] through changes in membrane potential. 7. The results are consistent with the idea that intravascular pressure causes membrane potential depolarization, which opens voltage-dependent Ca(2+) channels, acting as ‘voltage sensors’, thus increasing Ca(2+) entry and arterial wall [Ca(2+)], which leads to vasoconstriction

Histamine decreases myogenic tone in rat cerebral arteries by H-2-receptor-mediated K-v channel activation, independent of endothelium and cyclic AMP

The effect of histamine on the pressure-induced constriction was characterized in rat cerebral arteries and mechanisms were investigated. Rat cerebral arteries were pressurized to 70 mm Hg in an arteriograph and the effect of histamine on myogenic tone was studied. Histamine and amthamine, a selective histamine H-2-receptor agonist, concentration-dependently decreased myogenic tone, which was unchanged in the absence of endothelium. 2-(2-aminoethyl) pyridine, a selective histamine H-1-receptor agonist, produced concentration-dependent constriction of arteries that was significantly increased in the absence of endothelium. Imetit, a selective histamine H-3-receptor agonist, has no effect on myogenic tone. The dilation to histamine was antagonized by tiotidine, a selective antagonist of histamine H-2-receptor subtype, giving a pK(B) of 7.86 that was not altered in the absence of endothelium. The histamine-mediated dilation was significantly antagonized by NF449, a reversible inhibitor of Gs-protein activation but was not affected by ODQ and SQ 22536. Dilations to histamine and amthamine were accompanied by a decrease in arterial wall calcium measured by fura-2 ratios. The dilation to histamine was significantly reduced by partial depolatization of smooth muscle by 25 mM KCl (control 91 +/- 5%, 25 mM KCI 53 +/- 5%, P <0.002) and was not observed in the presence of strongly depolarizing 60 mM KCI. The histamine dilation was not affected by iberiotoxin, barium chloride and glibenclamide but was strongly antagonized by 4-aminopyridine (0.3 mM) and tetraethylammonium chloride (10 mM) (pEC(50): control: 5.6 +/- 0.14-aminopytidine: 4.1 +/- 0.1 (P <0.001); tetraethylammonium, chloride: 3.2 +/- 0.2 (P <0.0001)). These results suggest that histamine-mediated reversal of myogenic tone in rat cerebral arteries is endothelium-independent, mediated by histamine H-2-receptor subtype with no involvement of guanylyl cyclase or adenylyl cyclase activation and most likely involves activation of K-V potassium channels. (c) 2006 Elsevier B.V. All rights reserved