Influence of neonatal sympathectomy on proximal renal resistance artery function in spontaneously hypertensive rats

Abstract

Renal transplantation experiments have shown that the kidney contributes to chronic sympathectomy-induced arterial pressure reduction in spontaneously hypertensive rats (SHR). The underlying mechanisms are currently unclear but may include alterations in the function of small renal arteries. Neonatal SHR were sympathectomized by intraperitoneal guanethidine injections and removal of adrenal medullary tissue. Controls were sham- or hydralazine-treated. At 12 weeks of age, distal interlobar artery segments were investigated using small-vessel wire myography. Vessels from sympathectomized animals showed increased sensitivity to noradrenaline (NE). Vasopressin- and endothelin-1-induced vasoconstriction was similar in all groups (as reflected by the pD(2), i.e. -logEC(50), where EC(50) is the molar concentration of agonist eliciting a half-maximal response). Maximum vasopressin-induced tension was similar in all groups while endothelin-1-induced maximum tension was significantly higher in sympathectomized than in sham-treated SHR. The sensitivity of NE-induced vasoconstriction to extracellular Ca(2+) did not differ between groups while sensitivity to L-type Ca(2+) channel activation was significantly higher in both sympathectomized and hydralazine-treated animals than in sham-treated animals. Endothelium-dependent and independent vasodilation were similar in all groups. Sequential blockade of NO-synthase and cyclooxygenase had similar effects in all groups. In conclusion, neonatal sympathectomy does not induce any changes in the function of isolated proximal renal resistance arteries from SHR that could explain the blood pressure lowering effect of a kidney graft from sympathectomized SHR.

Impaired coronary function in Wistar Ottawa Karlsburg W rats—a new model of the metabolic syndrome

“…Skeletal muscle arteries were obtained from the hindlimbs (gracilis artery). In some experiments, renal (distal second-order branches of the renal artery) and mesenteric arteries (third-order branches) were investigated, and dissection was performed as described previously [9,10]. All vessels were investigated in a model 410A small vessel wire myograph (J.P. Trading, Aarhus, Denmark) under isometric conditions as described previously [9,10].…”

“…All vessels were investigated in a model 410A small vessel wire myograph (J.P. Trading, Aarhus, Denmark) under isometric conditions as described previously [9,10]. Data were acquired and analyzed with LabView-based software Myodaq/Myodata (Maastricht University, Maastricht, Netherlands) [9,10].…”

“…In some experiments, renal (distal second-order branches of the renal artery) and mesenteric arteries (third-order branches) were investigated, and dissection was performed as described previously [9,10]. All vessels were investigated in a model 410A small vessel wire myograph (J.P. Trading, Aarhus, Denmark) under isometric conditions as described previously [9,10]. Data were acquired and analyzed with LabView-based software Myodaq/Myodata (Maastricht University, Maastricht, Netherlands) [9,10].…”

The Kidney as a Determinant of Genetic Hypertension

“…However, we found no evidence for an influence of neonatal sympathectomy on proximal renal resistance artery function in SHR that would persist after renal transplantation, and that might explain the differences in blood pressure between F1 hybrid recipients of an SHR kidney from neonatally sympathectomized versus hydralazine-treated donors. 20 As outlined above, the results of experimental renal transplantation studies show that the genetic background of the kidney graft is a major determinant of blood pressure in the recipients, sometimes clearly overriding other factors. They also show that nongenetic factors may persistently change the renal set point for arterial pressure, and they finally show that nonrenal mechanisms contribute importantly to genetic hypertension.…”

Neonatal sympathectomy reduces NADPH oxidase activity and vascular resistance in spontaneously hypertensive rat kidneys

“…These results indicate that neonatal sympathectomy induces a persistent reduction in RVR that is maintained for at least several weeks after restoration of the extrarenal neurohormonal environment by means of kidney transplantation. Detailed investigation of isolated distal interlobar artery function from SHR did not reveal major effects of neonatal sympathectomy (11). Therefore, it is likely that major effects of sympathectomy on renal preglomerular vessel function are exerted at the level of interlobular arteries or afferent arterioles.…”