Venous Tone in the Developmental Stages of Spontaneous Hypertension

Abstract

Abstract —The initial stages of hypertension in the spontaneously hypertensive rat (SHR) are characterized by an increase in cardiac output. Venous capacitance plays an important role in the control of cardiac output. This study tested the hypothesis that venous tone is elevated in the developmental stages of spontaneous hypertension. Male SHR or normotensive Wistar-Kyoto (WKY) rats were instrumented for the measurement of arterial pressure (FAP) and intrathoracic vena caval pressure (FVP). A latex-tipped catheter was advanced into the right atrium via the jugular vein. Mean circulatory filling pressure (MCFP), an index of integrated venomotor tone, was calculated as MCFP=FVP+(FAP−FVP)/VAR. FAP and FVP were recorded after 5 seconds of right atrial balloon inflation. The venous to arterial compliance ratio (VAR) was estimated as 76 for WKY and 106 for SHR. Mean arterial pressure (MAP), heart rate, and MCFP were recorded in conscious rats of 4 to 6 and 8 to 10 weeks of age. In 4- to 6-week-old rats, both MAP and MCFP were significantly elevated in the SHR (MAP, 129±6 mm Hg; MCFP, 6.6±0.4 mm Hg) compared with the age-matched WKY (MAP, 91±6 mm Hg; MCFP, 5.4±0.4 mm Hg), whereas heart rate was not significantly different. The elevations in MAP (SHR, 144±4 mm Hg; WKY, 102±3 mm Hg) and MCFP (SHR, 7.7±0.3 mm Hg; WKY, 6.0±0.2 mm Hg) in SHR were exaggerated at 8 to 10 weeks of age. After ganglionic blockade (chlorisondamine; 10 mg/kg), the differences in MCFP were no longer statistically significant between SHR and WKY at both 4 to 6 weeks of age (3.9±0.2 versus 4.0±0.3 mm Hg) and 8 to 10 weeks of age (5.0±0.3 versus 4.3±0.3 mm Hg, respectively). The differences in MAP at 4 to 6 weeks of age (79±7 versus 67±5 mm Hg, respectively) also were not statistically significant after ganglionic blockade. However, a significant difference in MAP between strains remained after ganglionic blockade in 8- to 10-week-old rats (90±5 versus 63±3 mm Hg, respectively). These findings indicate that venous tone is increased via autonomic effector systems during the developmental stages of spontaneous hypertension. These data also suggest that autonomic mechanisms predominate at very early stages, whereas nonautonomic mechanisms assume more importance in maintaining the elevated MAP as hypertension progresses.