Cardiac sympathetic dysfunction in the prehypertensive spontaneously hypertensive rat

Area of Science:

• Cardiovascular Physiology
• Neuroscience
• Hypertension Research

Background:

• Prehypertensive spontaneously hypertensive rats (SHR) exhibit altered stellate neuron activity, including larger calcium transients and reduced norepinephrine transporter (NET) activity.
• The functional implications of these cellular changes for peripheral sympathetic responsiveness in young SHR remain unclear.

Purpose of the Study:

• To investigate whether peripheral sympathetic responsiveness is exaggerated in young (4-week-old) SHR compared to Wistar-Kyoto (WKY) controls.
• To determine the role of norepinephrine transporter activity and neuronal calcium signaling in enhanced cardiac sympathetic function in prehypertension.

Main Methods:

• In vivo and in vitro physiological assessments of arterial pressure and heart rate responses to autonomic stimulation.
• Measurement of radiolabeled norepinephrine [(3)H]NE release from isolated atrial preparations.
• Quantification of plasma neuropeptide Y levels via ELISA.
• Pharmacological blockade of NET and alpha2-adrenergic receptors to assess norepinephrine reuptake and signaling pathways.

Main Results:

• While in vivo arterial pressure was similar between SHR and WKY rats, SHR exhibited significant tachycardia.
• Isolated atrial preparations from SHR showed greater tachycardia upon right stellate stimulation and increased [(3)H]NE release compared to WKY.
• Plasma neuropeptide Y levels were elevated in SHR atria.
• Desipramine (NET inhibitor) normalized [(3)H]NE release differences, while yohimbine (α2-antagonist) did not.

Conclusions:

• Prehypertensive SHR display enhanced cardiac sympathetic neurotransmission and responsiveness.
• Reduced norepinephrine reuptake via NET activity contributes significantly to this exaggerated sympathetic response.
• These findings highlight an intrinsic sympathetic hyperresponsiveness in the SHR model of hypertension, originating at the peripheral end-organ level.