The paraventricular nucleus of the hypothalamus (PVN) is an important integrative site in autonomic and neuroendocrine control of cardiovascular system. Its role in the regulation of sympathetic outflow depends upon an interplay of at least 30 identified inhibitory and excitatory neurotransmitters. A number of those neurotransmitters produce their effects by changing the activity of neuronal cAMP-dependent protein kinase. We hypothesize that, by selectively blocking the cAMP-dependent protein kinase, we can modulate PVN neuronal activity involved in autonomic cardiovascular control. All experimental procedures in this study conformed to 86/609/EEC. Experiments were performed in conscious male normotensive Wistar rats and spontaneously hypertensive (SHR) rats, equipped with radiotelemetric device for registration of cardiovascular parameters and bilaterally microinjected into the PVN with adenovirus to overexpress selective cAMP-dependent protein kinase inhibitor-protein kinase inhibitor alpha (PKIα) or eGFP (control). Surgical procedures were performed under combined ketamine (100 mg kg-1, i.m.) and xylazine (10 mg kg-1, i.m.) anesthesia. Seven days after in vivo gene transfer rats were recorded both under baseline conditions and during exposure to acute air-jet stress. Blood pressure (BP), heart rate (HR) and their short-term variabilities (BPV and HRV) as well as spontaneous baroreflex sensitivity (BRS) were evaluated using spectral analysis and the sequence method, respectively. Values are expressed as mean±SEM. One-way ANOVA for repeated measures followed by Bonferroni post hoc test was used to assess differences between groups. Differences were taken as significant at p<0.05. Both under baseline and stressful conditions, overexpression of PKIα in the PVN of Wistar rats (n=6) induced significant decrease in mean values of systolic BP (BASELINE: 96±5 mmHg vs. 116±4 mmHg for control Wistars; STRESS: 120±1 mmHg vs. 136±2 mmHg for control Wistars, p<0.05 respectively), compared to control Wistar rats (n=6). Moreover, overexpression of PKIα in the PVN of Wistar rats increased BRS (3.9±1 ms mmHg-1 vs. 1.9±0.09 ms mmHg-1 for control Wistars, p<0.05), reduced total systolic BPV (2.29±0.22 mmHg2 vs. 3.26±0.3 mmHg2 for control Wistars, p<0.05) due to decrease in low frequency of systolic BP (0.38±0.07 mmHg2 vs. 0.97±0.27 mmHg2 for control Wistars, p<0.05) and induced decrease in LF/HF-HR ratio (0.18±0.09 vs. 1.21±0.28 for control Wistars, p<0.05) at rest. Overexpression of PKIα in the PVN of SHRs (n=6) did not induce any significant changes in BP, HR and their variabilities compared to non-transfected SHRs (n=6). These data suggest that cAMP-dependent protein kinase signaling in the PVN may be important in modulation of cardiovascular autonomic activity and baroreflex function.