Altered Vascular Resistance Properties and Acute Pressure-Natriuresis Mechanism in Neonatal and Weaning Spontaneously Hypertensive Rats

Abstract

Abstract-Although it has been extensively scrutinized, the factor(s) involved in the initiation and development of hypertension in spontaneously hypertensive rats (SHRs) remains unresolved. The objective of the present study was to determine whether, early in development, the causal mechanism(s) for the development of hypertension in young SHRs involves an integration of 2 processes, specifically an upregulation of structurally based vascular resistance properties and a rightward shift in the hemodynamic component of pressure-natriuresis. Mean arterial pressure was determined in conscious 4-week-old SHRs and Wistar-Kyoto rats via previously implanted aortic catheters. Structurally based hindlimb vascular resistance properties were assessed in 2-and 4-week-old SHRs and Wistar-Kyoto rats. Renal interstitial hydrostatic pressure was measured after short-term manipulations of renal arterial pressure (RAP) in 4-week-old, anesthetized rats. Although mean arterial pressure in conscious SHRs (113Ϯ5 mmHg) and Wistar-Kyoto rats (110Ϯ6 mmHg) was not significantly different at 4 weeks of age, SHRs at 2 and 4 weeks of age already had increases in structurally based vascular resistance properties of Ϸ30% above age-and weight-matched Wistar-Kyoto rats. Furthermore, the acute RAP-renal interstitial hydrostatic pressure relationship was found to be linear in both strains, and the temporal coupling of the stimulus to response was rapid; that is, renal interstitial hydrostatic pressure responses to changes in RAP were Ͻ2 s. Although the slope of the RAP-renal interstitial hydrostatic pressure relationship was not significantly different between strains, the relationship was significantly shifted (18%) to higher RAPs in SHRs. These results suggest that alterations in both vascular structure and renal function in young SHRs occur before elevations in mean arterial pressure. A lthough the factors responsible for the initiation and development of genetic hypertension have been extensively studied in the spontaneously hypertensive rat (SHR), the basis and time course for blood pressure elevation remain enigmatic. Specifically, what remains controversial is whether the 2 most widely studied processes, vascular abnormalities and renal dysfunction, lead to increases in arterial pressure or vice versa.Since the 1970s, 1 it has been well established that vascular abnormalities, such as increases in vascular resistance, vascular reactivity to vasoconstrictors, and media:lumen ratio, are associated with hypertension in the adult SHR.1-3 Despite the number of studies describing vascular morphometric and histological differences in young SHRs, 4-9 evidence linking blood pressure elevations with vascular structural and functional changes remains unresolved in the neonatal and weaning SHRs. The hypothesis that vascular structural changes antecede and initiate a rise in arterial pressure has been disputed for 2 main reasons, the presence 8,10-13 or lack 4-7,9,14,15 of blood pressure elevation in studies of young SHRs and substantial differences be...

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