Impaired recovery of vascular smooth muscle intracellular calcium following agonist stimulation in insulin resistant (Zucker obese) rats.
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)
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Department of Physiology Program, University of Tennessee, Knoxville 37996-1900.
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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
D007328:Insulin; C049925:fura-2-am; D000804:Angiotensin II; D001127:Arginine Vasopressin; D000252:Calcium-Transporting ATPases; D002118:Calcium; D016257:Fura-2