Calcitonin gene-related peptide (CGRP) and substance P (SP) play counter-regulatory roles in coronary flow. This study is to assess whether effects of CGRP and SP are gender-specific.
Methods
Langendorff-perfused hearts were used to compare coronary flow rates among 119 wild-type, α-CGRP and SP receptor knockout mice under various perfusion pressures (20, 30, 40, 50 mmHg).
Results
For mouse heart coronary flow rate, deletion of α-CGRP gene resulted in significant reduction for both genders at all pressures; female CGRP knockout showed 15.3% reduction (P < .01); male CGRP knockout showed 13.8% reduction (P < .01); no significant difference between male and female CGRP knockout; female SP receptor knockout showed 13.9% increase (P < .01); female SP receptor knockout had a greater percentage decrease than male (P < .01).
Conclusions
CGRP plays similar roles as a vasodilator in males and females. SP seems to act as a vasoconstrictor in females.
LeeS.E., KimJ.H.Involvement of substance P and calcitonin gene-related peptide in development and maintenance of neuropathic pain from spinal nerve injury model of rat.Neurosci Res.2007; 58: 245–249.
2.
ElshourbagyN.A., AdamouJ.E., SwiftA.M.Molecular cloning and characterization of the porcine calcitonin gene-related peptide receptor.Endocrinology.1998; 139: 1678–1683.
3.
OnuohaG.N., AlparE.K.Calcitonin gene-related peptide and other neuropeptides in the plasma of patients with soft tissue injury.Life Sci.1999; 65: 1351–1358.
4.
HouL., LiW., WangX.Mechanism of interleukin-1 beta-induced calcitonin gene-related peptide production from dorsal root ganglion neurons of neonatal rats.J Neurosci Res.2003; 73: 188–197.
5.
HooverD.B., ChangY., HancockJ.C., ZhangL.Actions of tachykinins within the heart and their relevance to cardiovascular disease.Jpn J Pharmacol.2000; 84: 367–373.
6.
UrsellP.C., RenC.L., AlbalaA., DaniloP.Jr.. Nonadrenergic noncholinergic innervation. Anatomic distribution of calcitonin gene-related peptide-immunoreactive tissue in the dog heart.Circ Res.1991; 68: 131–140.
7.
BörzseiR., PozsgaiG., BagolyT.Inhibitory action of endomorphin-1 on sensory neuropeptide release and neurogenic inflammation in rats and mice.Neuroscience.2008; 152: 82–88.
8.
AyI., TuncerM.Both endothelium and afferent nerve endings play a role in acetylcholine-induced renal vasodilation.Life Sci.2006; 79: 877–882.
9.
HumpelC., SariaA.Characterization of neurokinin binding sites in rat brain membranes using highly selective ligands.Neuropeptides.1993; 25: 65–71.
10.
IgweO.J.c-Src kinase activation regulates preprotachykinin gene expression and substance P secretion in rat sensory ganglia.Eur J Neurosci.2003; 18: 1719–1730.
11.
BloomquistE.I., KreamR.M.Leukotriene D4 acts in part to contract guinea pig ileum smooth muscle by releasing substance P.J Pharmacol Exp Ther.1987; 240: 523–528.
12.
WimalawansaS.J.Calcitonin gene-related peptide and its receptors: molecular genetics, physiology, pathophysiology, and therapeutic potentials.Endocr Rev.1996; 17: 533–585.
13.
BlockM.L., LiG., QinL.Potent regulation of microgliaderived oxidative stress and dopaminergic neuron survival: substance P vs. dynorphin.Faseb J.2006; 20: 251–258.
14.
WangL.H., LuoM., WangY., GalliganJ.J., WangD.H.Impaired vasodilation in response to perivascular nerve stimulation in mesenteric arteries of TRPVl-null mutant mice.J Hypertens.2006; 24: 2399–2408.
15.
ValdermarssonS., Ikomi-KummJ., MontiM.Thyroid hormones and thermogenesis: a microcalorimetric study of overall cell metabolism in lymphocytes from patients with different degrees of thyroid dysfunction.Acta Endocrinol (Copenh).1990; 123: 155–160.
16.
LanluaP., BukoskiR.D., WimalawansaS.J., YallampalliC.Effects of pregnancy and female sex steroid hormones on calcitonin gene-related peptide content of mesenteric artery in rats.Biol Reprod.2002; 67: 1430–1434.
17.
GangulaP.R., WimalawansaS.J., YallampalliC.Sex steroid hormones enhance hypotensive effects of calcitonin gene-related Peptide in aged female rats.Biol Reprod.2002; 67: 1881–1887.
18.
DePalatisL.R., KhorramO., McCannS.M.Age-, sex-, and gonadal steroid-related changes in immunoreactive substance P in the rat anterior pituitary gland.Endocrinology.1985; 117: 1368–1373.
19.
AukesA.M., BishopN., GodfreyJ., CipollaM.J.The influence of pregnancy and gender on perivascular innervation of rat posterior cerebral arteries.Reprod Sci.2008; 15: 411–419.
20.
SamniahN., VoelckelW.G., ZielinskiT.M.Feasibility and effects of transcutaneous phrenic nerve stimulation combined with an inspiratory impedance threshold in a pig model of hemorrhagic shock.Crit Care Med.2003; 31: 1197–1202.
21.
HouM., UddmanR., TajtiJ., EdvinssonL.Nociceptin immunoreactivity and receptor mRNA in the human trigeminal ganglion.Brain Res.2003; 964: 179–186.
22.
McCullochJ., UddmanR., KingmanT.A., EdvinssonL.Calcitonin gene-related peptide: functional role in cerebrovascular regulation.Proc Natl Acad Sci U S A.1986; 83: 5731–5735.
23.
EdvinssonM.L., EdvinssonL.Comparison of CGRP and NO responses in the human peripheral microcirculation of migraine and control subjects.Cephalalgia.2008; 28: 563–566.
24.
FlourisA.D., MetsiosG.S., JamurtasA.Z., KoutedakisY.Sexual dimorphism in the acute effects of secondhand smoke on thyroid hormone secretion, inflammatory markers and vascular function.Am J Physiol Endocrinol Metab.2008; 294: E456–E462.
25.
FieldS.B., BurneyI.A., NeedhamS., MaxwellR.J., GriffithsJ.R.From hydralazine to CGRP to man?Int J Hyperthermia.1994; 10: 451–455.
26.
TirapelliC.R., LeoneA.F., YogiA.Ethanol consumption increases blood pressure and alters the responsiveness of the mesenteric vasculature in rats.J Pharm Pharmacol.2008; 60: 331–341.
27.
AaltoY., ForsgrenS., KjorellU., BerghJ., FranzenL., HenrikssonR.Enhanced expression of neuropeptides in human breast cancer cell lines following irradiation.Peptides.1998; 19: 231–239.
28.
ShimozawaN., OkajimaK., HaradaN.Estrogen and isoflavone attenuate stress-induced gastric mucosal injury by inhibiting decreases in gastric tissue levels of CGRP in ovariectomized rats.Am J Physiol Gastrointest Liver Physiol.2007; 292: G615–G619.
29.
LamariY., GhorbelM., GarelJ.M.Effects of 17 betaestradiol on calcitonin and calcitonin-gene-related peptide secretions and contents in a murine medullary thyroid carcinoma C-cell line (CA-77).Reprod Nutr Dev.1995; 35: 655–661.
30.
HuangA., SunD., KaleyG., RollerA.Estrogen preserves regulation of shear stress by nitric oxide in arterioles of female hypertensive rats.Hypertension.1998; 31(1 Pt 2): 309–314.
YaoitaH., SatoE., KawaguchiM., SaitoT., MaeharaK., MaruyamaY.Nonadrenergic noncholinergic nerves regulate basal coronary flow via release of capsaicin-sensitive neuropeptides in the rat heart.Circ Res.1994; 75: 780–788.
33.
WangL., WangD.H.TRPV1 gene knockout impairs postischemic recovery in isolated perfused heart in mice.Circulation.2005; 112: 3617–3623.
34.
LeeW.I., XuY., FungS.M., FungH.L.eNOS-dependent vascular interaction between nitric oxide and calcitonin gene-related peptide in mice: gender selectivity and effects on blood aggregation.Regul Pept.2003; 110: 115–122.
35.
LiD., PengJ., XinH.Y., LuoD., ZhangY.S., ZhouZ., JiangD.J., DengH.W., LiY.J.Calcitonin gene-related peptide-mediated antihypertensive and anti-platelet effects by rutaecarpine in spontaneously hypertensive rats.Peptides.2008; 29(10): 1781–1788.
