Aortas Isolated from Sinoaortic‐Denervated Rats Exhibit Rhythmic Contractions That Are Regulated by Pharmacologically Distinct Calcium Sources

Abstract

Sinoaortic denervation is characterized by arterial pressure lability, without sustained hypertension. Aortas isolated from rats with sinoaortic denervation present rhythmic contractions. We studied the participation of distinct Ca 2+ sources in the maintenance of the oscillations. Three days after the surgeries, aortic rings were placed in an organ chamber, and the incidence of aortas presenting rhythmic contractions was measured. Specific drugs were employed to analyse the participation of the Ca 2+ released from the sarcoplasmic reticulum [2-APB (diphenylborinic acid 2-aminoethyl ester), thapsigargin and ryanodine] and external Ca 2+ entry [Bay K 8644, verapamil and DMB (dimethylbenzyl amiloride)] on the rhythmic contractions. Additionally, we verified the effects of chloride channel blocker NPPB [5-nitro-2-(3-phenylpropylamino)-benzoic acid] on the maintenance of the rhythmic contractions. Under phenylephrine stimulus, sinoaortic-denervated rat aortas exhibited rhythmic contractions in the frequency of 4.5 ± 0.50 cycles/min. and an amplitude of 0.465 ± 0.05 g. 2-APB, thapsigargin and ryanodine inhibited the rhythmic contractions. Bay K 8644 increased the oscillations, reaching maximum values with a concentration of 50 nM (18.5 ± 2.5 cycles/min.). The rhythmic contractions were inhibiting by verapamil and Ca 2+ -free solution. DMB and NPPB did not alter the oscillations. In conclusion, we observed that aorta isolated from sinoaortic-denervated rats present rhythmic contractions. Moreover, drugs that impaired intracellular Ca Cytosolic calcium concentration ([Ca 2+ ] c ) has a central role in controlling the vascular smooth muscle tone. The resting [Ca 2+ ] c in smooth muscle cells is around 100 nM [1,2]. In response to excitatory agonists, which produce InsP 3 , it increases by several hundredfold in a few minutes [3]. In the majority of cases, the increase in [Ca 2+ ] c can be attributed to Ca 2+ release from sarcoplasmic reticulum, which is considered to be the main cytosolic Ca 2+ store in vascular smooth muscle cells [4] and to Ca 2+ entry (via plasmalemmal Ca 2+ channels, pumps and exchangers) from the extracellular space [5].Smooth muscle is frequently classified by the manner in which it responds to excitatory stimulation. Therefore, tonic smooth muscle such as that often found in vasculature, airways, gastrointestinal and urogenital systems responds to contractile agonists by producing a simple steady contraction. In contrast, many previous studies have shown that some isolated smooth muscle preparations generate rhythmic contractions, as in the case of the rat portal vein [6], the subcutaneous artery of the dog [7], the bovine mesenteric vein [8], the rabbit urethra [9], the rat urinary bladder [10], the porcine thoracic duct [11] and bronquia [12], and many arteries from hypertensive rats [13][14][15][16].The effects of rhythmic contractions on the vascular beds are currently controversial and hence their physiological significance has yet to be correctly defined. In an atte...

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“…Briefly, in these experiments, aortic segments were exposed to Ca 2+ ‐free medium (CFM) containing (in mmol/L): NaCl 118; KCl 4.7; MgSO 4 ·7H 2 O 1.2; NaH 2 PO 4 1.2; NaHCO 3 25; EGTA 2; glucose 11. Transient contractions to a submaximal dose of PE (10 −6 mol/L) were evaluated in the presence or absence of the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) reuptake inhibitor thapsigargin (10 −6 mol/L) 10 or the Ca 2+ channel blocker nifedipine (10 −6 mol/L) 11 . After the PE‐induced vasoconstriction had reached a plateau in PSS, the medium was switched to CFM (depletion period) for 15 min, after which time the CFM was switched to PSS (repletion period) for 15 min and then switched to CFM again.…”