Vasoconstriction In Vascular Beds Research Articles

Effect of the Calcimimetic, Cinacalcet, on Regional Vascular Resistance and Blood Ionized Calcium in Uremic and Normal Rats

Cinacalcet (CIN) decreases serum PTH and Ca in ESRD patients with SHPT and also produces acute elevations in blood pressure (BP) in uremic rats. To test the hypothesis that CIN produces acute hypertension through vasoconstriction of multiple vascular beds, the regional hemodynamic effects of CIN were delineated in anesthetized rats and correlated to changes in BP and iCa2+. Male SD rats were subjected to 5/6 nephrectomy (NX) or no surgery (Normal); at 7–8 weeks uremia rats were instrumented to record BP, heart rate and regional blood flow (carotid, mesenteric, hindlimb). CIN (1, 3, 10 mg/kg; 30 min/dose) or VEH was infused over 90 min. Change from baseline in CIN vs. VEH was analyzed by repeated measures ANOVA, Dunnett’s (∗p<0.05). In NX, CIN decreased iCa2+ from 1.22±0.02 mmol/L at baseline to 1.10±0.02∗, 0.97±0.02∗ and 0.91±0.03∗ mmol/L and produced increases in BP (from 119±6 mmHg to 129±5, 142±4∗, and 145±3∗ mmHg at the end of each infusion). At 1 mg/kg carotid (CVR) and mesenteric (MVR) vascular resistance increased to 16±6%∗ above baseline (VEH=3±2%) and 18±6∗% above baseline (VEH= −1±2%), respectively. Hindlimb (HVR) vascular resistance trended upward to 13±8% above baseline (VEH = −2±2%). At 3 mg/kg increases in CVR (38±10%∗), MVR (40±8%∗) and HVR (39±14%∗) were exacerbated; at 10 mg/kg values remained at or near these levels. The effects of CIN on iCa2+, BP and VR in Normal rats were similar to NX. Thus, at doses producing reductions in iCa2+ CIN acutely increases BP in uremic and non-uremic rats, responses that occur in parallel to vasoconstriction in vascular beds fed by the carotid, mesenteric, and hindlimb arteries.

Effects of the neuropeptide YY1 receptor antagonist SR 120107A on sympathetic vascular control in pigs in vivo .

The possible involvement of neuropeptide Y in sympathetic vasoconstriction in various vascular beds in anesthetized pigs in vivo was studied using the neuropeptide Y Y1 receptor antagonist SR 120107A. Single impulse sympathetic nerve stimulation evoked rapid vasoconstrictor responses in hind limb and nasal mucosa which were not affected by SR 120107A (1.5 mg kg-1). Vascular responses to high frequency stimulation was measured in kidney, spleen (three 1 s bursts at 20 Hz or 300 impulses at 10 Hz), hind limb and nasal mucosa (three 1 s bursts at 20 Hz). High frequency stimulation evoked rapid vasoconstriction in all vascular beds studied. This was followed by a long-lasting phase of reduced blood flow in hind limb and nasal mucosa. SR 120107A (1.5 mg kg-1) attenuated the vasoconstriction evoked by the 20 Hz stimulation in the kidney, whereas a higher dose (a total of 6.0 mg kg-1) was required to reduce the vascular response in kidney to the 10 Hz simulation. SR 120107A (1.5 mg kg-1) did not inhibit the vascular responses in spleen, hind limb or nasal mucosa to the 20 Hz stimulation or the vasoconstriction in the spleen to the 10 Hz stimulation (a total of 6 mg kg-1). Subsequent addition of the adrenoceptor antagonists phenoxybenzamine (5 mg kg-1) plus timolol (2 mg kg-1) strongly reduced the vascular responses to single impulse stimulation and high frequency stimulation (20 Hz series) in all vascular beds. We conclude that endogenous neuropeptide Y acting on the neuropeptide Y Y1 receptor, as revealed by SR 120107A, is likely to account for part of the sympathetic vasoconstriction upon high frequency stimulation in the kidney.

Vasoconstrictor effects of galanin and distribution of galanin containing fibres in three species of elasmobranch fish

Galanin is found in perivascular sympathetic neurons in a wide range of vertebrate species. In placental mammals, galanin has either no effect on blood pressure, or weak depressor effects, but in other vertebrates it has been shown to be a potent pressor agent. To investigate how extensive the vasoconstrictor effects of galanin may be in the vertebrates, the vascular effects of galanin were tested in two species of shark, Heterodontus portusjacksoni, and Hemiscyllium ocellatum, and a ray, Rhinobatos typus. Nerve fibres showing immunoreactivity to galanin were located surrounding gut blood vessels, but were absent from branchial efferent arteries in all three species. Intravenous injection of galanin caused a significant rise in caudal arterial blood pressure in H. portusjacksoni and H. ocellatum, but no change in R. typus. Contraction of segments of pancreatico-mesenteric artery were measured in an organ bath also. Galanin (10 −6 M) caused 21–38% of the maximum K + induced contraction in all species, but no response in efferent branchial arteries from R. typus. In conclusion, in three elasmobranchs, a galanin-like peptide is present in perivascular nerve fibres, and galanin causes differential vasoconstriction in vascular beds. These data extend the number of vertebrate groups in which galanin has been shown to be a vasoconstrictor peptide.