title: Impaired recovery of vascular smooth muscle intracellular calcium following agonist stimulation in insulin resistant (Zucker obese) rats.
abstract: We have previously shown that insulin attenuates vasoconstrictor responses to pressor agonists and accelerates vascular smooth muscle cell (VSMC) Ca(2+)-ATPase mediated Ca2+ efflux and vascular relaxation. We have now sought to determine if VSMC from insulin resistant (Zucker Obese, ZO) rats manifest exaggerated [Ca2+]i responses to pressor agonists and impaired [Ca2+]i recovery (rate of [Ca2+]i return to baseline) compared to their lean controls (ZL). Thoracic aortae from ZO and ZL were enzymatically digested to release VSMC (n = 16 animals/group and 8 determinations/group). Freshly dispersed cells were washed, counted, and loaded with Fura-2-AM. The [Ca2+]i responses to and rate of recovery from angiotensin II (AII; 200 nmol/L) and arginine vasopressin (AVP; 10 mumol/L) were studied fluorometrically in stirred suspension (10(6) cells/mL). Peak [Ca2+]i responses to AVP were not significantly different in ZO v ZL, while responses to AII were higher in ZL ([Ca2+]i, 180 +/- 7 v 160 +/- 4% of baseline in ZL and ZO, P < .02). Since we have recently shown insulin to increase AII-releasable Ca2+ stores in sarcoplasmic reticulum, this increase in peak [Ca2+]i response to AII in ZL may reflect relative VSMC insulin resistance in ZO. Despite their increased peak AII response, ZL exhibited a more rapid recovery from both the AII-stimulated load (recovery rate, 66.1 +/- 8.9 v 42.1 +/- 9.0 nmol/L/min in ZL and ZO, P < .02) and the AVP-stimulated [Ca2+]i load (22.2 +/- 2.3 v 18.4 +/- 4.6 nmol/L/min).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Physiology Program, University of Tennessee, Knoxville 37996-1900.
authors.forename: M A
authors.initials: MA
authors.lastname: Abel
authors.forename: M B
authors.initials: MB
authors.lastname: Zemel
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000166:cytology; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000502:physiology; D002478:Cells, Cultured; D005470:Fluorometry; D016257:Fura-2 / Q000031:analogs & derivatives; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism* / Q000502:physiology; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D011924:Rats, Zucker; D012519:Sarcoplasmic Reticulum / Q000737:chemistry / Q000201:enzymology; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D007328:Insulin; C049925:fura-2-am; D000804:Angiotensin II; D001127:Arginine Vasopressin; D000252:Calcium-Transporting ATPases; D002118:Calcium; D016257:Fura-2