Biomedical subjects

Timothy Roy

Publications and source records attributed to Timothy Roy.

3 recordsLinked to original sources

PubMed2005

Effects of systemic and local phenylephrine and arginine vasopressin infusions in conscious postnatal sheep.

Mean arterial pressure (MAP) increases after birth, however, the mechanisms remain unclear. Systemic angiotensin II (ANG II) infusions increase MAP in newborn sheep, but the direct effects of ANG II on peripheral vascular resistance (PVR) are minimal. Thus, its systemic pressor effects may reflect release of other pressor agents, e.g. alpha-agonists and/or AVP, suggesting they contribute to postnatal regulation of MAP and PVR. To address this, we performed studies in conscious sheep at 7-14, 15-21, and 22-35 d postnatal, infusing phenylephrine (PE) or AVP systemically or intra-arterially into the hindlimb while measuring MAP, heart rate (HR), and femoral blood flow (FmBF). Basal MAP and FmBF rose, whereas HR and femoral vascular resistance (FmVR) fell (p < or = 0.03) during the first month postnatal. Although systemic PE and AVP dose dependently increased MAP and FmVR and decreased FmBF and HR (p < 0.001, ANOVA) at all ages, responses were not age dependent. Notably, increases in FmVR exceeded increases in MAP, and responses to PE appeared to exceed AVP (p < 0.05). Hindlimb infusions of both agents decreased FmBF and increased FmVR dose dependently (p < 0.001, ANOVA) at all ages without altering MAP or HR. These responses also were not age dependent. Unlike ANG II, PE and AVP directly increase PVR in newborn sheep. Moreover, FmVR increases more than MAP at all doses, suggesting these agonists may contribute to postnatal MAP regulation and could mediate the effects of systemic ANG II on postnatal MAP.

Angiotensin II↗

PubMed2002

Mechanisms modulating estrogen-induced uterine vasodilation.

Estrogen, a potent vasodilator, has its greatest effects in reproductive tissues, e.g., increasing uterine blood flow (UBF) 5- to 10-fold within 90 min after a bolus dose. High-conductance potassium channels and nitric oxide (NO) contribute to the uterine responses, but other factors may be involved. We examined the role of ATP-dependent (ATP-sensitive) and voltage-gated (Kv) potassium channels and new protein synthesis in ovariectomized ewes with uterine artery flow probes, infusing intraarterial inhibitors glibenclamide (GLB; KATP), 4-aminopyridine (4-AP; Kv) or cycloheximide, respectively, into one uterine horn before and/or after systemic estradiol-17 beta (E2 beta, 1 microgram/kg i.v.). E2 beta alone increased UBF > 5-fold and heart rate by 10-25% (P < .01) within 90 min; mean arterial pressure (MAP) was unaffected. GLB did not alter basal hemodynamic parameters or responses to E2 beta. Basal UBF and heart rate were unaffected by 4-AP, but MAP increased by 10% and 25% at 30 and 120 min of infusion (P < .01), respectively. Although E2 beta-induced rises in UBF were unaffected in the control uterine horn, 4-AP dose-dependently inhibited UBF responses in the infused horn (R = .83, P = .003, n = 10). Cycloheximide not only dose-dependently inhibited UBF responses (R = .57, P = .01, n = 18) and increases in uterine cGMP secretion, 23.4 +/- 10.7 versus 340 +/- 60 pmol/min (P < .001), but also decreased UBF by 50% and cGMP by approximately 90% at the time of maximum UBF. Mechanisms modulating estrogen-induced uterine vasodilation involve signaling pathways that include NO, smooth muscle cGMP, smooth muscle potassium channels and new protein synthesis.

Animals↗

PubMed2002

Differential responses to systemic and local angiotensin II infusions in conscious postnatal sheep.

Angiotensin II (ANG II) increases blood pressure (MAP) via specific ANG II receptors (AT) and is considered important in regulating MAP after birth. In adult animals, AT(1) receptors predominate in vascular smooth muscle (VSM) and mediate vasoconstriction. In newborn sheep, AT(2) receptors, which do not mediate vasoconstriction, predominate in vascular smooth muscle until 2 wk postnatal when they are replaced by AT(1). Thus, the mechanisms whereby ANG II increases MAP after birth are unclear. We examined the effects of ANG II on femoral vascular resistance (FmVR) and blood flow (FmBF) in serial studies of newborn sheep (n = 7) at 7-14 d, 15-21 d, and 22-35 d. Animals had femoral catheters implanted for systemic ANG II infusions and cardiovascular monitoring, and a flow probe was implanted on the contralateral artery proximal to the superficial saphenous artery, which contained a catheter for intra-arterial ANG II infusions. Studies were performed using a range of systemic and intra-arterial ANG II doses. Systemic ANG II increased MAP dose-dependently at all ages (p < 0.001); however, responses were not age dependent. FmBF rose dose dependently at 7-14 d (p < 0.001) and was unchanged at older ages. FmVR was unaffected at 7-14 d, but values increased dose dependently at 15-21 d and 22-3 5d (p < 0.001), although never exceeded relative increases in MAP. Local ANG II did not alter MAP, FmBF, or FmVR at any age. Although systemic ANG II increases MAP and FmVR dose dependently after birth, ANG II-induced vasoconstriction is attenuated. Furthermore, intra-arterial ANG II does not alter FmVR in the absence of systemic responses, suggesting incomplete vascular smooth muscle AT(1) expression, stimulation of local ANG II antagonists, or ANG II-mediated release of another vasoconstrictor.

Angiotensin II↗