Diminished mesenteric vaso- and venoconstriction and elevated plasma ANP and BNP with simulated microgravity

Abstract

Diminished constriction of arteries and veins following exposure to microgravity or bed rest is associated with a reduced ability to augment peripheral vascular resistance (PVR) and stroke volume during orthostasis. We tested the hypothesis that small mesenteric arteries and veins, which are not exposed to large pressure shifts during simulated microgravity via head-down tail suspension (HDT), will exhibit decrements in adrenergic constriction after HDT in rats. Small mesenteric arteries and veins from control (Con; n = 41) and HDT (n = 35) male Sprague-Dawley rats were studied in vitro. Vasoactive responsiveness to norepinephrine (NE) in arteries (10(-9) to 10(-4) M) and veins (pressure-diameter responses from 2 to 12 cmH(2)O after incubation in 10(-6) or 10(-4) M NE) were evaluated. Plasma concentrations of atrial (ANP) and NH(2)-terminal prohormone brain (NT-proBNP) natriuretic peptides were also measured. In mesenteric arteries, sensitivity and maximal responsiveness to NE were reduced with HDT. In mesenteric veins there was a diminished venoconstriction to NE at any given pressure in HDT. Plasma concentrations of both ANP and NT-proBNP were increased with HDT, and maximal arterial and venous constrictor responses to NE after incubation with 10(-7) M ANP or brain natriuretic peptide (BNP) were diminished. These data demonstrate that, in a vascular bed not subjected to large hydrodynamic differences with HDT, both small arteries and veins have a reduced responsiveness to adrenergic stimulation. Elevated levels of circulating ANP or NT-proBNP could adversely affect the ability of these vascular beds to constrict in vivo and conceivably could alter the intrinsic constrictor properties of these vessels with long-term exposure.

Figure 1

Concentration-response relation of norepinephrine in mesenteric resistance arteries from Control and Head-down tilt (HDT) animals. Values are means ± SE. *HDT significantly different from that of Control (P<0.05).

Figure 2

Pressure-diameter responses after exposure to norepinephrine in small mesenteric veins from Control and HDT animals. A) Diameter was smaller in mesenteric veins from Control animals at all pressures with norepinephrine, and exposure to 10⁻⁴ M norepinephrine resulted in smaller diameters versus those at 10⁻⁶ M norepinephrine (P<0.05). B) Mesenteric veins from HDT animals showed smaller diameters at all pressures with exposure to norepinephrine (P<0.05). Only at 4, 6, and 8 cm H₂0 was a difference observed between the diameters measured at 10⁻⁶ versus 10⁻⁴ M norepinephrine (P<0.05). Values are means ± SE.

Figure 3

The percent constriction of mesenteric veins from Control and HDT rats to A) 10⁻⁶ M norepinephrine and B) 10⁻⁴ M norepinephrine. Values are means ± SE. *HDT significantly different from that of Control (P<0.05).

Figure 4

A) Plasma atrial natriuretic peptide (ANP) and B) brain-type natriuretic peptide (NT-proBNP) concentrations in Control (n=28) and HDT (n=26) rats. Values are means ± SE. †P=0.052 between groups. *P<0.05 between groups.

Figure 5

A) Dose-response relations of mesenteric arteries to norepinephrine pre- and post-incubation in either ANP (10⁻⁷ M) or BNP (10⁻⁷ M). B) Dose-response relations of mesenteric veins to norepinephrine pre- and post-incubation in either ANP (10⁻⁷ M) or BNP (10⁻⁷ M). Values are means ± SE. *P<0.05 vs. control constrictor response at a given concentration of norepinephrine. †P<0.05 vs. constrictor response after incubation in ANP at a given concentration of norepinephrine.