Functional alterations of mesenteric small resistance arteries in Milan hypertensive and normotensive rats.
The Milan hypertensive rat strain (MHS) is a genetic strain in which cardiovascular phenotypes seem to be dependent, at least in part, on adducin gene polymorphisms. The aim of our study was to evaluate the structure, contractile responses and endothelium-dependent vasodilation in mesenteric small resistance arteries in 12-week-old MHS, (n=7), age-matched Milan normotensive rats (MNS, n=7) and congenic strains in which the DNA segments carrying the alpha-adducin locus from the MHS have been introgressed into the MNS (MNA, n=7). Systolic blood pressure (tail cuff) and left ventricular weight to body weight were measured. Mesenteric small arteries were dissected and mounted on a micromyograph; the media:lumen ratio was then calculated. Concentration-response curves to acetylcholine and to norepinephrine (NE) were created. Systolic blood pressure was significantly increased in the MHS and MNA strains compared with the MNS. No significant difference in mesenteric small resistance artery structure was observed among the groups; however, a slightly more elevated media:lumen ratio was observed in MNA compared with the MNS. In contrast, left ventricular weight to body weight was significantly increased and ACH-induced dilatation was significantly impaired in the MHS and in MNA compared with MNS. The concentration-response curve to NE in the MHS showed significantly reduced sensitivity to NE; however, maximum contraction was increased in the MHS vs. the other groups. The MHS presents cardiac (but not vascular) remodeling, endothelial dysfunction and a peculiar contractile response to NE, compared with the other groups. The systolic blood pressure increase and trend to vascular remodeling in MNA support the pathogenic role of alpha-adducin.
Rizzoni
Damiano
D
Department of Medical and Surgical Sciences, University of Brescia, Clinica Medica, Brescia, Italy. rizzoni@med.unibs.it
Castellano
Maurizio
M
Porteri
Enzo
E
Giacchè
Mara
M
Ferrari
Patrizia
P
Cusi
Daniele
D
De Ciuceis
Carolina
C
Boari
Gianluca E M
GE
Rosei
Enrico Agabiti
EA
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002148:Calmodulin-Binding Proteins / Q000235:genetics / Q000502:physiology; D004247:DNA / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D006973:Hypertension / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008638:Mesenteric Arteries / Q000473:pathology*; D009119:Muscle Contraction / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009206:Myocardium / Q000473:pathology; D051381:Rats; D014655:Vascular Resistance / Q000235:genetics* / Q000502:physiology*; D014662:Vasoconstrictor Agents; D014664:Vasodilation / Q000502:physiology; D014665:Vasodilator Agents; D000099291:Adducins
D002148:Calmodulin-Binding Proteins; D004247:DNA; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000099291:Adducins